WO2005018742A1 - Method and aparatus for optimization of collimator angles in intensity modulated radiation therapy treatment - Google Patents

Method and aparatus for optimization of collimator angles in intensity modulated radiation therapy treatment Download PDF

Info

Publication number
WO2005018742A1
WO2005018742A1 PCT/US2004/025922 US2004025922W WO2005018742A1 WO 2005018742 A1 WO2005018742 A1 WO 2005018742A1 US 2004025922 W US2004025922 W US 2004025922W WO 2005018742 A1 WO2005018742 A1 WO 2005018742A1
Authority
WO
WIPO (PCT)
Prior art keywords
collimator
leaf
value
leaf collimator
target
Prior art date
Application number
PCT/US2004/025922
Other languages
French (fr)
Inventor
Duan Q. Wang
Robert W. Hill
Simon Chun-Pin Lam
Original Assignee
Nomos Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34221355&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2005018742(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Nomos Corporation filed Critical Nomos Corporation
Publication of WO2005018742A1 publication Critical patent/WO2005018742A1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/103Treatment planning systems
    • A61N5/1031Treatment planning systems using a specific method of dose optimization
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/103Treatment planning systems
    • A61N5/1036Leaf sequencing algorithms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1042X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy with spatial modulation of the radiation beam within the treatment head

Definitions

  • the invention relates to a method and apparatus for intensity modulated radiation therapy treatment, and more specifically, a method and apparatus for optimization of collimator angles for multileaf collimators ("MLC”) used in intensity modulated radiation therapy treatment.
  • MLC multileaf collimators
  • the beams eye view is a view from the perspective of the opening in the multi-leaf collimator along an axis of the radiation beam.
  • the number of segments are considered reduced when adjacent segments have substantially the same intensity level.
  • a reduction in MU's is a reduction in the amount of radiation delivered to the target.
  • Embodiments of the present invention utilize a new algorithm to determine collimator angles in favoring, or enhancing, IMRT radiation therapy treatment plan delivery efficiency.
  • the number segments and MUs can be reduced using the set of collimator angles determined by utilizing the new algorithm, without compromising treatment plan quality.
  • Embodiments of the present invention also include a cost function obtained by combining the prior algorithm based upon Brahme's orientation theory with the algorithm utilized in the present invention.
  • embodiments of the present invention include a method and apparatus that provide benefits to certain MLCs currently in use, since the method and apparatus of the present invention seek to minimize the maximum travel distance of MLC leaf pairs.
  • advantageously methods are provided to determine a collimator angle of a multi-leaf collimator having an opening and a plurality of multi-leaf collimator pair leafs for closing portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments to apply radiation to a tumor target.
  • an embodiment of the present convention includes a method, preferably being computer-implemented, which includes calculating an initial radiation beam arrangement according to a desired prescription to determine a radiation beam delivery angle (gantry angle of rotation for a linear accelerator).
  • This radiation beam arrangement is updated or changed by incorporating a first function, generally in the form of a cost function, to determine an optimum collimator angle of the multi-leaf collimator.
  • the first cost function includes both a second cost function designed to enhance delivery efficiency by reducing at least one of a number of radiation beam segments and reducing a number of radiation beam monitor units required for delivery of the desired prescription, and a third cost function to enhance conformity of the radiation beam arrangement to a target shape as viewed through the opening in the multi-leaf collimator. This view from the perspective of the opening in the multi-leaf collimator along an axis of the radiation beam defines a beams eye view of the multi-leaf collimator.
  • the collimator angle selection need not stop at the first iteration of computing the first function.
  • the change or update in the radiation beam arrangement can be rejected if the change of the radiation beam arrangement significantly leads to a lesser correspondence to the desired prescription.
  • weights applied to the second and third functions can be adjusted.
  • the change or update of the radiation beam arrangement is generally accepted if the change of the radiation beam arrangement both leads to more radiation delivery efficiency and does not lead to significantly less correspondence to the desired prescription.
  • a method includes first determining a treatment plan according to a desired prescription.
  • a value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator is then determined for each one of a plurality of discrete collimator angles.
  • a value of a maximum effective length for a multi-leaf collimator pair leaf of the plurality of multi-leaf collimator pair leafs having the maximum effective length can also be determined for each one of the plurality of discrete collimator angles.
  • a sum of the value of the area difference and the value of the maximum effective length for each of the plurality of discrete collimator angles is then determined.
  • a minimum sum value for the sum of the value of the area difference and the value of the maximum effective length for the collimator angle of the plurality of collimator angles having the minimum sum value is then further determined. An analysis utilizing this function leads to the identification of the collimator angle best suited for application to the treatment plan prior to treatment plan optimization.
  • weights can be assigned to the maximum effective length and area difference. By applying a first weight value to the maximum effective length and a second weight value to the area difference prior to determining the minimum sum value, a different collimator angle can be deemed the optimum angle.
  • a similar method includes providing a function, preferably in the form of a cost function, having a first delivery efficiency portion providing for enhanced radiation delivery efficiency and a second target conformity portion providing for enhanced target conformity.
  • a preference can be selected between delivery efficiency and target conformity by assigning weights to the delivery efficiency and target conformity portions of the function.
  • the first delivery efficiency portion of the function includes a delivery efficiency function that determines at each of a plurality of discrete collimator angles a weighted value of a maximum effective length for a multi-leaf collimator pair leaf of the plurality of multi-leaf collimator pair leafs having the maximum effective length.
  • the second target conformity portion of the function includes a target conformity function that determines at each of a plurality of discrete collimator angles a weighted value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the beams eye view of the multi-leaf collimator.
  • a value for the cost function at a selected radiation beam delivery angle incorporating the selected preference is then determined. Determination of the function value directly leads to the determination of the optimum collimator angle at this given radiation beam delivery angle. Because a target is typically treated utilizing multiple radiation beam delivery angles (gantry angles of rotation on a linear accelerator), this process of determining an optimum collimator angle can be repeated for each selected radiation beam delivery angle.
  • an embodiment of the present invention can be in the form of a computer readable medium that is readable by a computer determining a collimator angle of a multi-leaf collimator having an opening and a plurality of multi-leaf collimator pair leafs for closing portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments to apply radiation to a tumor target.
  • the computer readable medium includes a set of instructions that, when executed by the computer, causes the computer to perform various operations such as determining a treatment plan according to a desired prescription, determining for each one of a plurality of discrete collimator angles a value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator, and determining for each one of the plurality of discrete collimator angles a value of a maximum effective length for a multi-leaf collimator pair leaf of the plurality of multi- leaf collimator pair leafs having the maximum effective length.
  • the instructions can also include determining a sum of the value of the area difference and the value of the maximum effective length for each of the plurality of discrete collimator angles, and a minimum sum value for the sum of the value of the area difference and the value of the maximum effective length for the collimator angle of the plurality of collimator angles having the minimum sum value. This determination allows for the selection of an optimum collimator angle for application to the treatment plan, typically implemented prior to treatment plan optimization. [0015]
  • embodiments of the present invention also include an apparatus for use in conformal radiation therapy of a target tumor.
  • the apparatus can include a multi-leaf collimator having a plurality of selectable discrete collimator angles, an opening to pass a radiation beam, and a plurality of multi-leaf collimator pair leafs to close portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments.
  • the apparatus can also include a computer in communication with the multi-leaf collimator to form the radiation beam arrangement incorporating a function to determine a collimator angle of the multi-leaf collimator to thereby enhance the radiation beam arrangement.
  • the function includes parameters to enhance delivery efficiency by reducing a number of segments and reducing a number of monitor units required for delivery of a desired radiation prescription.
  • These parameters can include a value of a maximum effective length for a multi-leaf collimator pair leaf of the plurality of multi-leaf collimator pair leafs having the maximum effective length.
  • the function can also include parameters to enhance conformity of the radiation beam arrangement to a shape of the target as viewed through the opening in the multi-leaf collimator, a view from the perspective of the opening in the multi-leaf collimator along an axis of the radiation beam defining a beams eye view of the multi-leaf collimator.
  • These parameters can include a value of an area difference between an area of an opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with a target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the beams eye view of the multi-leaf collimator.
  • the apparatus can further include means for selecting a first weight value for the maximum effective length and a second weight value for the area difference, and means for applying the first weight value to the maximum effective length and the second weight value to the area difference prior to determining the minimum sum value.
  • this allows the user to prioritize between delivery efficiency and target conformity.
  • FIG. 1 is a beams eye view (“BEV”) of a target looking through a MLC;
  • FIG. 2 is a beams eye view through a MLC of a target according to an embodiment of the present invention
  • FIG. 3 is a chart comparing the number of segments and MUs between radiation therapy treatment plans using the prior art and the present invention
  • FIG. 4 is a chart comparing prostate conformity index between radiation therapy treatment plans using the prior art and the present invention.
  • FIG. 5 is a chart of a comparison of a seminal vesicle conformity index between radiation therapy treatment plans using the prior art and the present invention
  • FIG. 6 is a chart of a comparison of seminal vesicles inhomogenity index between radiation therapy treatment plans using the prior art and the present invention
  • FIG. 7 is a chart of a comparison of prostate inhomogenity index between radiation therapy treatment plans using the prior art and the present invention.
  • FIG. 8 is a table illustrating results of a non-clinical treatment plan with a cube target
  • FIG. 9 is a table of results for a non-clinical treatment plan with an ellipsoid target
  • FIG. 10 are BEVs of a cube as a target
  • FIG. 11 are BEVs of an ellipsoid as a target
  • FIG. 12 is a chart comparing the number of segments and MUs between radiation therapy treatment plans using the prior art and the present invention.
  • FIG. 13 is a chart comparing the conformity index of a prostate between radiation therapy treatment plans using the prior art and the present invention.
  • FIG. 14 is a comparison of a conformity index for seminal vesicles between radiation therapy treatment plans using the prior art and the present invention;
  • FIG. 15 is a table summarizing the results of the charts of FIGS. 13 and 14;
  • FIG. 16 is a comparison of the number of segments and MUs when utilizing the prior art and the present invention.
  • FIG. 17 is a cross-sectional view of the MLC illustrating leafs forming a plurality of radiation beam segments.
  • FIG. 1 illustrates the desired results of a presently used treatment plan using an algorithm based upon Brahme's theory, wherein the conformity for targets, or lesions, 20 is prioritized.
  • Present treatment planning systems mathematically minimize the area between the frame 21 shaped by a conventional MLC opening and the edge of the target 20.
  • Multi-leaf collimators (MLCs) currently in use with which the present invention may be utilized such as, for example, the multi-leaf collimator 40 depicted in FIG. 17, include, among others, MLCs manufactured and/or distributed by Varian Medical Systems, Inc., such as its Millennium MLC Models No. MLC-120, MLC-80, and MLC- 52, which correspond to MLCs having 120, 80, and 52 leaves; and/or MLCs of Siemens AG and/or Siemens Medical Systems, Jnc.
  • the algorithm utilized in embodiments of the present invention is based upon two hypotheses: (1) that the maximum number of segments in a radiation beam is dominated, or determined, by the MLC leaf pair of a plurality of leaf pairs 41 (FIG. 17) which delivers the maximum number of beamlets, or radiation beamlets; and (2) that the number of segments in a pair of MLC leaves is proportional to an effective leaf travel distance (the number of pencil beamlets) defined by:
  • n is the number of separated target regions in the path of the MLC leaf pair, or leaf travel distance of an individual MLC leaf pair
  • m t is the leaf travel distance in the ith isolated target region for the MLC leaf pair
  • k is the weight factor to account for multi isolated regions in the path over which the MLC leaf pair sweeps.
  • the collimator angles are chosen so that the maximum amount of movement in individual MLC leaf pairs, at a certain collimator angle, is a minimum, as the maximum number of segments in a beam is largely determined by the MLC leaf pair which performs the maximum number of segments.
  • ( ⁇ ) is the collimator angle varying from 0 to 180, 1 degree/step, and ( ⁇ 0 ), is the optimized angle.
  • the procedure is to search the maximum effective length of MLC pairs in a certain collimator angle, and then find the minimum values from, in this example, the 180 maximum effective lengths.
  • ⁇ ( ⁇ ) is the area difference between what an MLC can define and the target area
  • a and B are weight factors used in the algorithm to select a focus between delivery efficiency and conformity.
  • the computations associated with the cost function to determine the optimum collimator angle and related software 43 can be processed on a computer or other computational device known to those skilled in the art and which can be associated with the selected radiation delivery apparatus.
  • computer 45 (FIG. 17) generally having a processor 47 and memory 49, and software 43 stored in the memory 49, can be used for such purpose.
  • Computer 45 can include various input devices and/or displays (not shown) or function as a server connected to a remote terminal.
  • Computer 45 is typically connected to a controller 51 to control the multi-leaf collimator 40. Further, the software 43 to perform such computations can be stored on various other forms of storage media known to those skilled in the art, such as, for example, computer hard drives, compact discs, and removable drives, and is preferably associated with the treatment planning software.
  • the area, which the MLC can define is outlined by lines 30, which is the rectangular shaped area defined by the MLC leaves, and the target area 31 is shown as having an irregular shape defined by lines 32.
  • the user of the method and apparatus of embodiments of the present invention can choose what is preferred by adjusting the weight factors A and B.
  • radiation treatment plans using intensity modulated radio surgery may prefer to treat a patient with a system utilizing the algorithm based upon Brahme's theory.
  • IMRS intensity modulated radio surgery
  • the reduction of the number of segments and MUs might be prioritized.
  • the reduction of the number of segments and MUs which are indicative of IMRT delivery efficiency, relies upon the shape and size of the target or targets, and the number of modulation levels utilized.
  • the following illustrates a case for the treatment of prostate cancer, two targets (the prostate and the seminal vesicles) and three organs at risk (“OAR"s) (the rectum, bladder, and femoral heads) are contoured. Seven radiation beams, ten modulation levels, and a six MV linear accelerator are used.
  • the number of segments was reduced forty-two (42%) percent, twenty-nine (29%) percent, and twenty-six (26%) percent and the number of MUs were reduced forty-one (41%) percent, thirty-five (35%) percent and thirty-four (34%) percent, when 102 leaf, 80 leaf, and 52 leaf MLCs of Varian Medical Systems, Inc., were used, respectively, as shown in FIG. 3.
  • the number of MUs and segments, as well as angle differences from JJVIRT treatment plans utilizing the method and apparatus of the present invention, including the new algorithm are compared with treatment plans utilizing the algorithm based upon Brahme's theory. In FIG. 3, all values are normalized by the values used in the treatment plan with Brahme's algorithm.
  • the comparison includes a thirty two (32%) percent segment reduction and an MU reduction of fourteen (14%) percent with a Siemens MLC utilizing IMF AST® computer software of Siemens Medical Systems, Inc. It can also be seen that the larger the angle differences between plans utilizing the two algorithms, the greater reduction of the number of segments of MUs. Still with reference to FIG. 3, the "angle difference" is defined as the ratio of the collimator angle difference in the treatment plans utilizing the new algorithm and the Brahme's algorithm to that 90 times the number of beams.
  • Two sets of IMRT radiation therapy treatment plans were generated with two target shapes, a cube and an ellipsoid.
  • the number of segments and MUs were compared when the collimator angle was set at either where the l e was a minimum or a maximum.
  • the amount of segmentation and MU reduction which can be achieved by manipulating the collimator angle alone are illustrated in connection with FIGS. 8 and 9 for different MLC leaf-sequencing algorithms and different sizes of the pencil beamlets, as will be hereinafter described in greater detail.
  • a three dimensional target such as a cube or ellipsoid, are projected onto two dimensions.
  • the JJVTRT radiation therapy treatment planning system utilized in connection with FIGS. 8-11 is a CORVUS ® 5 planning system of NOMOS Corporation.
  • the collimator angle is set at 0, the MLC leafs move along 90 degrees in the IEC cordinate system utilized by CORVUS ® 5.
  • the target in both sets of plans was prescribed a dosage of 2Gy and with no margin for uncertainties.
  • the optimizer of the CORVUS 5 was a continuous am ealer.
  • the first set of plans used a 100 mm cube as a target, with no OARs.
  • the gantry angles were chosen so that the projections of the cube in the BEV have different dimension ratios (minimum dimension/maximum dimension).
  • Five beams were used at gantry angles of 0, 67, 85, 135, and 169 degrees, which correspond to dimension ratios of 1.4, 1.6, 1.7, 1.5, and 1.47.
  • the collimator angles in the plans when l e is a minimum or 90 degrees while 45, 41, 38, 43, and 44 degrees resulted in maximum 4.
  • the results for the first set of treatment plans with a cube target are set forth in the table of FIG.
  • the treatment plan formulated with the STANDARDTM leaf-sequencing algorithm for a 120 leaf MLC of Varian Medical Systems, Inc. (0.5 x 0.5 cm pencil beamlet) and a Varian 80 leaf MLC (1 x 1 cm beamlet) have the largest segmentation and MU reduction (34 percent and 26 percent, respectively) when setting the collimator angle with the algorithm utilized in the method and apparatus of the present invention.
  • the treatment plan is based upon the IMF AST® leaf- sequencing algorithm of Siemens with a Siemens 54 leaf MLC, the reduction of segments and MUs is less significant.
  • FIGS. 12-16 show the results of two clinical cases which were investigated, those being a prostate and a complicated head and neck case.
  • the prostate case had two targets, the prostate and seminal vesicles, and three OARs, which were the bladder, rectum, and femoral heads.
  • the total target volume was 170 cc. Seven beams and eleven modulation levels were used.
  • the optimizer again was a continuous annealer and no margin was given to the targets and OARs.
  • the collimator angle similarity was defined by:
  • ( ⁇ j ) is the collimator angle difference at individual gantry angles between using the Brahme's algorithm and the algorithm of the present invention
  • j is the number of beams.
  • CI target conformity indexes
  • FIGS. 13 and 14 The target conformity indexes ("CI") for both prostate and seminal vesicles are illustrated in the graphs of FIGS. 13 and 14, and in tabular form in FIG. 15.
  • the improvement in conformity index for MLCs directed by treatment plans using the new algorithm was more significant for MLCs directed by treatment plans utilizing the Brahme's algorithm and having a lower conformity index.
  • the method and apparatus of the present invention can reduce the number of segments and MUs without compromising the treatment plan quality.
  • the reduction of the number of segments and MUs is generally more effective for: (1) the STANDARDTM leaf-sequencing algorithm based on the work of Bortfeld for the Varian MLC; (2) large targets; and (3) small pencil beamlets.
  • the results from the non-clinical and clinical cases would appear to show that treatment plans using the IMF AST® leaf-sequencing algorithm do not obtain as much reduction of MUs and segments as those using the STANDARDTM algorithm.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Radiation-Therapy Devices (AREA)

Abstract

A method and apparatus to determine an optimum collimator angle of a multi-leaf collimator having an opening and multiple leaf pairs for closing portions of the opening to form a radiation beam arrangement having multiple radiation beam segments. The method and apparatus include application of a cost function to determine a collimator angle which provides for delivery efficiency and target conformity. The user can preferentially either selectively enhance delivery efficiency of the radiation beam arrangement, reducing a number of radiation beam segments and reducing a number of radiation beam monitor units required for delivery of the desired prescription, or selectively enhance conformity of the radiation beam arrangement to a target shape. The optimum collimator angle is then used for delivery of an optimized radiation beam arrangement to a patient by a radiation delivery device.

Description

METHOD AND APPARATUS FOR OPTIMIZATION OF COLLIMATOR ANGLES IN INTENSITY MODULATED RADIATION THERAPY TREATMENT
BACKGROUND OF THE INVENTION
1. Related Applications
[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application Serial No. 60/494,222 filed August 11, 2003, and U.S. Non-Provisional Patent Application filed August 11, 2004, both entitled "Method and Apparatus for Optimization of Collimator Angles in Intensity Modulated Radiation Therapy Treatment."
2. Information Incorporated by Reference
[0002] Applicant incorporates by reference U.S. Patent No. 5,596,619, entitled "Method and Apparatus for Conformal Radiation Therapy", issued January 21, 1997, and U.S. Patent No. 5,802,136, entitled "Method and Apparatus for Conformal Radiation Therapy", issued September 1, 1998, which are both commonly assigned to the assignee of the present invention.
3. Field of the Invention
[0003] The invention relates to a method and apparatus for intensity modulated radiation therapy treatment, and more specifically, a method and apparatus for optimization of collimator angles for multileaf collimators ("MLC") used in intensity modulated radiation therapy treatment.
4. Description of the Related Art
[0004] When determining collimator angles in intensity modulated radiation therapy treatment, or intensity modulated radiotherapy, ("EVIRT") inverse treatment plans for use with a MLC radiation delivery system, the most common practice currently is to select collimator rotation angles so that the MLC can be best conformed to the shape of the target, or lesion, in the radiation beam's eye view, or beams eye view ("BEV"). The algorithm used is based upon Brahme's orientation theory, by which the conformity for targets is prioritized. When using this algorithm, no consideration is given to delivery efficiency, e.g., reduction of the number of segments and monitor units ("MU"). Note, the beams eye view is a view from the perspective of the opening in the multi-leaf collimator along an axis of the radiation beam. Note also, the number of segments are considered reduced when adjacent segments have substantially the same intensity level. A reduction in MU's is a reduction in the amount of radiation delivered to the target.
[0005] Accordingly, prior to the development of the present invention, there has been no method or apparatus for determining the collimator angle before optimization in inverse treatment planning system, which favors, or enhances delivery efficiency, such as by reducing the number of segments and MUs.
[0006] Therefore, the art has sought a method and apparatus for determining the collimator angle before optimization in an inverse treatment planning system which favors, or enhances, the delivery efficiency by reducing the number of segments and MUs. SUMMARY OF THE INVENTION
[0007] In accordance with the invention, the foregoing advantages have been achieved through the present method and apparatus for optimization of collimator angles in JJVIRT inverse treatment planning systems. Embodiments of the present invention utilize a new algorithm to determine collimator angles in favoring, or enhancing, IMRT radiation therapy treatment plan delivery efficiency. The number segments and MUs can be reduced using the set of collimator angles determined by utilizing the new algorithm, without compromising treatment plan quality. Embodiments of the present invention also include a cost function obtained by combining the prior algorithm based upon Brahme's orientation theory with the algorithm utilized in the present invention. Through use of embodiments of the present invention, including utilizing the new algorithm, the number of segments and MUs may be reduced, particularly for JJVIRT treatment planning systems currently in use. Advantageously, embodiments of the present invention include a method and apparatus that provide benefits to certain MLCs currently in use, since the method and apparatus of the present invention seek to minimize the maximum travel distance of MLC leaf pairs. [0008] More specifically, in embodiments of the present invention advantageously methods are provided to determine a collimator angle of a multi-leaf collimator having an opening and a plurality of multi-leaf collimator pair leafs for closing portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments to apply radiation to a tumor target. For example, an embodiment of the present convention includes a method, preferably being computer-implemented, which includes calculating an initial radiation beam arrangement according to a desired prescription to determine a radiation beam delivery angle (gantry angle of rotation for a linear accelerator). This radiation beam arrangement is updated or changed by incorporating a first function, generally in the form of a cost function, to determine an optimum collimator angle of the multi-leaf collimator. The first cost function includes both a second cost function designed to enhance delivery efficiency by reducing at least one of a number of radiation beam segments and reducing a number of radiation beam monitor units required for delivery of the desired prescription, and a third cost function to enhance conformity of the radiation beam arrangement to a target shape as viewed through the opening in the multi-leaf collimator. This view from the perspective of the opening in the multi-leaf collimator along an axis of the radiation beam defines a beams eye view of the multi-leaf collimator.
[0009] Advantageously, the collimator angle selection need not stop at the first iteration of computing the first function. The change or update in the radiation beam arrangement can be rejected if the change of the radiation beam arrangement significantly leads to a lesser correspondence to the desired prescription. For such occurrence, weights applied to the second and third functions can be adjusted. The change or update of the radiation beam arrangement, however, is generally accepted if the change of the radiation beam arrangement both leads to more radiation delivery efficiency and does not lead to significantly less correspondence to the desired prescription.
[0010] Also for example, in an embodiment of the present convention, a method includes first determining a treatment plan according to a desired prescription. A value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator is then determined for each one of a plurality of discrete collimator angles. A value of a maximum effective length for a multi-leaf collimator pair leaf of the plurality of multi-leaf collimator pair leafs having the maximum effective length can also be determined for each one of the plurality of discrete collimator angles. A sum of the value of the area difference and the value of the maximum effective length for each of the plurality of discrete collimator angles is then determined. A minimum sum value for the sum of the value of the area difference and the value of the maximum effective length for the collimator angle of the plurality of collimator angles having the minimum sum value, is then further determined. An analysis utilizing this function leads to the identification of the collimator angle best suited for application to the treatment plan prior to treatment plan optimization.
[0011] Depending upon the type or model of radiation delivery system carrying the multi-leaf collimator, the size and shape of the target, and/or whether efficiency or conformity or an intermediate mix thereof are assigned priority, weights can be assigned to the maximum effective length and area difference. By applying a first weight value to the maximum effective length and a second weight value to the area difference prior to determining the minimum sum value, a different collimator angle can be deemed the optimum angle.
[0012] In an embodiment of the present invention, a similar method includes providing a function, preferably in the form of a cost function, having a first delivery efficiency portion providing for enhanced radiation delivery efficiency and a second target conformity portion providing for enhanced target conformity. After preferably determining a type of radiation delivery system carrying the multi-leaf collimator and determining a size and a shape of the target, a preference can be selected between delivery efficiency and target conformity by assigning weights to the delivery efficiency and target conformity portions of the function. That is, the first delivery efficiency portion of the function includes a delivery efficiency function that determines at each of a plurality of discrete collimator angles a weighted value of a maximum effective length for a multi-leaf collimator pair leaf of the plurality of multi-leaf collimator pair leafs having the maximum effective length. The second target conformity portion of the function includes a target conformity function that determines at each of a plurality of discrete collimator angles a weighted value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the beams eye view of the multi-leaf collimator.
[0013] A value for the cost function at a selected radiation beam delivery angle incorporating the selected preference is then determined. Determination of the function value directly leads to the determination of the optimum collimator angle at this given radiation beam delivery angle. Because a target is typically treated utilizing multiple radiation beam delivery angles (gantry angles of rotation on a linear accelerator), this process of determining an optimum collimator angle can be repeated for each selected radiation beam delivery angle.
[0014] Advantageously, an embodiment of the present invention, can be in the form of a computer readable medium that is readable by a computer determining a collimator angle of a multi-leaf collimator having an opening and a plurality of multi-leaf collimator pair leafs for closing portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments to apply radiation to a tumor target. The computer readable medium includes a set of instructions that, when executed by the computer, causes the computer to perform various operations such as determining a treatment plan according to a desired prescription, determining for each one of a plurality of discrete collimator angles a value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator, and determining for each one of the plurality of discrete collimator angles a value of a maximum effective length for a multi-leaf collimator pair leaf of the plurality of multi- leaf collimator pair leafs having the maximum effective length. The instructions can also include determining a sum of the value of the area difference and the value of the maximum effective length for each of the plurality of discrete collimator angles, and a minimum sum value for the sum of the value of the area difference and the value of the maximum effective length for the collimator angle of the plurality of collimator angles having the minimum sum value. This determination allows for the selection of an optimum collimator angle for application to the treatment plan, typically implemented prior to treatment plan optimization. [0015] Advantageously, embodiments of the present invention also include an apparatus for use in conformal radiation therapy of a target tumor. The apparatus can include a multi-leaf collimator having a plurality of selectable discrete collimator angles, an opening to pass a radiation beam, and a plurality of multi-leaf collimator pair leafs to close portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments. The apparatus can also include a computer in communication with the multi-leaf collimator to form the radiation beam arrangement incorporating a function to determine a collimator angle of the multi-leaf collimator to thereby enhance the radiation beam arrangement. The function includes parameters to enhance delivery efficiency by reducing a number of segments and reducing a number of monitor units required for delivery of a desired radiation prescription. These parameters can include a value of a maximum effective length for a multi-leaf collimator pair leaf of the plurality of multi-leaf collimator pair leafs having the maximum effective length. The function can also include parameters to enhance conformity of the radiation beam arrangement to a shape of the target as viewed through the opening in the multi-leaf collimator, a view from the perspective of the opening in the multi-leaf collimator along an axis of the radiation beam defining a beams eye view of the multi-leaf collimator. These parameters can include a value of an area difference between an area of an opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with a target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the beams eye view of the multi-leaf collimator. The apparatus can further include means for selecting a first weight value for the maximum effective length and a second weight value for the area difference, and means for applying the first weight value to the maximum effective length and the second weight value to the area difference prior to determining the minimum sum value. Advantageously, this allows the user to prioritize between delivery efficiency and target conformity.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] So that the manner in which the features and advantages of the invention, as well as others which will become apparent, may be understood in more detail, a more particular description of the invention briefly summarized above may be had by reference to the embodiments thereof which are illustrated in the appended drawings, which form a part of this specification. It is to be noted, however, that the drawings illustrate only various embodiments of the invention and are therefore not to be considered limiting of the invention's scope as it may include other effective embodiments as well.
[0017] FIG. 1 is a beams eye view ("BEV") of a target looking through a MLC;
[0018] FIG. 2 is a beams eye view through a MLC of a target according to an embodiment of the present invention;
[0019] FIG. 3 is a chart comparing the number of segments and MUs between radiation therapy treatment plans using the prior art and the present invention;
[0020] FIG. 4 is a chart comparing prostate conformity index between radiation therapy treatment plans using the prior art and the present invention;
[0021] FIG. 5 is a chart of a comparison of a seminal vesicle conformity index between radiation therapy treatment plans using the prior art and the present invention;
[0022] FIG. 6 is a chart of a comparison of seminal vesicles inhomogenity index between radiation therapy treatment plans using the prior art and the present invention;
[0023] FIG. 7 is a chart of a comparison of prostate inhomogenity index between radiation therapy treatment plans using the prior art and the present invention;
[0024] FIG. 8 is a table illustrating results of a non-clinical treatment plan with a cube target;
[0025] FIG. 9 is a table of results for a non-clinical treatment plan with an ellipsoid target;
[0026] FIG. 10 are BEVs of a cube as a target;
[0027] FIG. 11 are BEVs of an ellipsoid as a target;
[0028] FIG. 12 is a chart comparing the number of segments and MUs between radiation therapy treatment plans using the prior art and the present invention;
[0029] FIG. 13 is a chart comparing the conformity index of a prostate between radiation therapy treatment plans using the prior art and the present invention; [0030] FIG. 14 is a comparison of a conformity index for seminal vesicles between radiation therapy treatment plans using the prior art and the present invention;
[0031] FIG. 15 is a table summarizing the results of the charts of FIGS. 13 and 14;
[0032] FIG. 16 is a comparison of the number of segments and MUs when utilizing the prior art and the present invention; and
[0033] FIG. 17 is a cross-sectional view of the MLC illustrating leafs forming a plurality of radiation beam segments.
DETAILED DESCRIPTION OF THE INVENTION
[0034] The present invention will now be described more fully hereinafter with reference to the accompanying drawings, which illustrate embodiments of the invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the illustrated embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like numbers refer to like elements throughout. Prime notation, if used, indicates similar elements in alternative embodiments.
[0035] FIG. 1 illustrates the desired results of a presently used treatment plan using an algorithm based upon Brahme's theory, wherein the conformity for targets, or lesions, 20 is prioritized. Present treatment planning systems mathematically minimize the area between the frame 21 shaped by a conventional MLC opening and the edge of the target 20. Multi-leaf collimators (MLCs) currently in use with which the present invention may be utilized, such as, for example, the multi-leaf collimator 40 depicted in FIG. 17, include, among others, MLCs manufactured and/or distributed by Varian Medical Systems, Inc., such as its Millennium MLC Models No. MLC-120, MLC-80, and MLC- 52, which correspond to MLCs having 120, 80, and 52 leaves; and/or MLCs of Siemens AG and/or Siemens Medical Systems, Jnc.
[0036] The algorithm utilized in embodiments of the present invention is based upon two hypotheses: (1) that the maximum number of segments in a radiation beam is dominated, or determined, by the MLC leaf pair of a plurality of leaf pairs 41 (FIG. 17) which delivers the maximum number of beamlets, or radiation beamlets; and (2) that the number of segments in a pair of MLC leaves is proportional to an effective leaf travel distance (the number of pencil beamlets) defined by:
/e = (l + ^ L-)∑ k f
wherein n is the number of separated target regions in the path of the MLC leaf pair, or leaf travel distance of an individual MLC leaf pair; mt is the leaf travel distance in the ith isolated target region for the MLC leaf pair; and k is the weight factor to account for multi isolated regions in the path over which the MLC leaf pair sweeps.
[0037] hi the algorithm used in embodiments of the present invention, the collimator angles are chosen so that the maximum amount of movement in individual MLC leaf pairs, at a certain collimator angle, is a minimum, as the maximum number of segments in a beam is largely determined by the MLC leaf pair which performs the maximum number of segments. The cost function to favor, or enhance, delivery efficiency, the reduction of segments, in determination of the collimator angle is: f(θ0) = minfmax le(θ)]}
where (θ) is the collimator angle varying from 0 to 180, 1 degree/step, and (θ0), is the optimized angle.
[0038] The procedure is to search the maximum effective length of MLC pairs in a certain collimator angle, and then find the minimum values from, in this example, the 180 maximum effective lengths. Combining the new algorithm utilized in embodiments of the present invention with the algorithm based upon Brahme's theory, the cost function to determine the collimator angle is: f(θ0)=min{A max[/e (θ)] + Bσ(θ)}
where σ(θ) is the area difference between what an MLC can define and the target area, and A and B are weight factors used in the algorithm to select a focus between delivery efficiency and conformity. [0039] The computations associated with the cost function to determine the optimum collimator angle and related software 43 (FIG. 17) can be processed on a computer or other computational device known to those skilled in the art and which can be associated with the selected radiation delivery apparatus. For example, computer 45 (FIG. 17) generally having a processor 47 and memory 49, and software 43 stored in the memory 49, can be used for such purpose. Computer 45 can include various input devices and/or displays (not shown) or function as a server connected to a remote terminal. Computer 45 is typically connected to a controller 51 to control the multi-leaf collimator 40. Further, the software 43 to perform such computations can be stored on various other forms of storage media known to those skilled in the art, such as, for example, computer hard drives, compact discs, and removable drives, and is preferably associated with the treatment planning software.
[0040] With reference to FIG. 2, the area, which the MLC can define, is outlined by lines 30, which is the rectangular shaped area defined by the MLC leaves, and the target area 31 is shown as having an irregular shape defined by lines 32.
[0041] The user of the method and apparatus of embodiments of the present invention can choose what is preferred by adjusting the weight factors A and B. For example, radiation treatment plans using intensity modulated radio surgery ("IMRS") may prefer to treat a patient with a system utilizing the algorithm based upon Brahme's theory. Alternatively, in a radiation therapy treatment plan for a large target or targets, the reduction of the number of segments and MUs might be prioritized.
[0042] The reduction of the number of segments and MUs, which are indicative of IMRT delivery efficiency, relies upon the shape and size of the target or targets, and the number of modulation levels utilized. For example, the following illustrates a case for the treatment of prostate cancer, two targets (the prostate and the seminal vesicles) and three organs at risk ("OAR"s) (the rectum, bladder, and femoral heads) are contoured. Seven radiation beams, ten modulation levels, and a six MV linear accelerator are used. Utilizing the method and apparatus of the present invention, the number of segments was reduced forty-two (42%) percent, twenty-nine (29%) percent, and twenty-six (26%) percent and the number of MUs were reduced forty-one (41%) percent, thirty-five (35%) percent and thirty-four (34%) percent, when 102 leaf, 80 leaf, and 52 leaf MLCs of Varian Medical Systems, Inc., were used, respectively, as shown in FIG. 3. hi FIG. 3, the number of MUs and segments, as well as angle differences from JJVIRT treatment plans utilizing the method and apparatus of the present invention, including the new algorithm, are compared with treatment plans utilizing the algorithm based upon Brahme's theory. In FIG. 3, all values are normalized by the values used in the treatment plan with Brahme's algorithm.
[0043] Still with reference to FIG. 3, the comparison includes a thirty two (32%) percent segment reduction and an MU reduction of fourteen (14%) percent with a Siemens MLC utilizing IMF AST® computer software of Siemens Medical Systems, Inc. It can also be seen that the larger the angle differences between plans utilizing the two algorithms, the greater reduction of the number of segments of MUs. Still with reference to FIG. 3, the "angle difference" is defined as the ratio of the collimator angle difference in the treatment plans utilizing the new algorithm and the Brahme's algorithm to that 90 times the number of beams.
[0044] With reference to FIGS. 4-7, a comparison of JJVIRT radiation treatment plans using the method and apparatus of the present invention, including the new algorithm, as compared with a treatment planning system using the Brahme's algorithm is illustrated in terms of target conformity and inhomogeneity indexes.
[0045] Two sets of IMRT radiation therapy treatment plans were generated with two target shapes, a cube and an ellipsoid. The number of segments and MUs were compared when the collimator angle was set at either where the le was a minimum or a maximum. The amount of segmentation and MU reduction which can be achieved by manipulating the collimator angle alone are illustrated in connection with FIGS. 8 and 9 for different MLC leaf-sequencing algorithms and different sizes of the pencil beamlets, as will be hereinafter described in greater detail.
[0046] Jn the beams eye view ("BEV") of the collimator, as shown in FIGS. 10 and 11, a three dimensional target, such a cube or ellipsoid, are projected onto two dimensions. The shortest dimension of the target is along the axis when 0 = 0. The JJVTRT radiation therapy treatment planning system utilized in connection with FIGS. 8-11 is a CORVUS®5 planning system of NOMOS Corporation. When the collimator angle is set at 0, the MLC leafs move along 90 degrees in the IEC cordinate system utilized by CORVUS®5. The target in both sets of plans was prescribed a dosage of 2Gy and with no margin for uncertainties. The optimizer of the CORVUS 5 was a continuous am ealer. The first set of plans used a 100 mm cube as a target, with no OARs. The gantry angles were chosen so that the projections of the cube in the BEV have different dimension ratios (minimum dimension/maximum dimension). Five beams were used at gantry angles of 0, 67, 85, 135, and 169 degrees, which correspond to dimension ratios of 1.4, 1.6, 1.7, 1.5, and 1.47. The collimator angles in the plans when le is a minimum or 90 degrees while 45, 41, 38, 43, and 44 degrees resulted in maximum 4. The results for the first set of treatment plans with a cube target are set forth in the table of FIG. 8, in which the ratio is defined as the value at the collimator angle when le is a minimum divided by that when le is a maximum. For the treatment plans with an ellipsoid target, the results are summarized in the table of FIG. 9. The treatment plan formulated with the STANDARD™ leaf-sequencing algorithm for a 120 leaf MLC of Varian Medical Systems, Inc. (0.5 x 0.5 cm pencil beamlet) and a Varian 80 leaf MLC (1 x 1 cm beamlet) have the largest segmentation and MU reduction (34 percent and 26 percent, respectively) when setting the collimator angle with the algorithm utilized in the method and apparatus of the present invention. When the treatment plan is based upon the IMF AST® leaf- sequencing algorithm of Siemens with a Siemens 54 leaf MLC, the reduction of segments and MUs is less significant.
[0047] In connection with clinical case studies, the following parameters are hereinafter defined below:
No. MU in the plan using the new algorithm • MU Ratio No. MU in the plan using Brehme's No. Segments in the plan with the new algorithm Seg. Ratio No. Segments in the plan using Brehme's
. Angle similarity = (1 - Colli.angledifferenceγ λ^% 90 * no.ofbeams
[0048] To further illustrate the advantages of the method and apparatus of the present invention incorporating the new algorithm, FIGS. 12-16 show the results of two clinical cases which were investigated, those being a prostate and a complicated head and neck case. The prostate case had two targets, the prostate and seminal vesicles, and three OARs, which were the bladder, rectum, and femoral heads. The total target volume was 170 cc. Seven beams and eleven modulation levels were used. The optimizer again was a continuous annealer and no margin was given to the targets and OARs. hi the prostate plan, the collimator angle similarity was defined by:
! ' (1_ =! — ) *ιoo 90* /
where (θj) is the collimator angle difference at individual gantry angles between using the Brahme's algorithm and the algorithm of the present invention, and j is the number of beams. With reference to FIG. 12, a comparison is illustrated of the ratio of the number of MUs, segments, and collimator angle similarity between the plan using Brahme's algorithm and that using the algorithm of the present invention, all values normalized by the values of the plan with Brahme's algorithm. The number of MUs and segments has been reduced dramatically utilizing the method and apparatus of the present invention incorporating the new algorithm.
[0049] The target conformity indexes ("CI") for both prostate and seminal vesicles are illustrated in the graphs of FIGS. 13 and 14, and in tabular form in FIG. 15. The improvement in conformity index for MLCs directed by treatment plans using the new algorithm was more significant for MLCs directed by treatment plans utilizing the Brahme's algorithm and having a lower conformity index.
[0050] In the complicated head and neck case, three large targets, totaling approximately 490cc, with 12 OARS, were the subject of an JJVIRT treatment plan. Seven beams and a continuous annealer were used. Eleven modulation levels were utilized, and no margin was given to either targets or OARS. The maximum dimension of the targets was 23.5 cm. The comparison of the number of MUs and segments, as well as the collimator angle similarity, is illustrated in the graph of FIG. 16. The less the collimator angle similarity, the more significant the reduction in MUs and segments with a treatment plan incorporating the new algorithm. [0051] In view of the foregoing non-clinical and clinical examples, it is seen that the method and apparatus of the present invention, utilizing the new algorithm herein, can reduce the number of segments and MUs without compromising the treatment plan quality. The reduction of the number of segments and MUs is generally more effective for: (1) the STANDARD™ leaf-sequencing algorithm based on the work of Bortfeld for the Varian MLC; (2) large targets; and (3) small pencil beamlets. The results from the non-clinical and clinical cases would appear to show that treatment plans using the IMF AST® leaf-sequencing algorithm do not obtain as much reduction of MUs and segments as those using the STANDARD™ algorithm.
[0052] Advantageously, since the algorithm of the method and apparatus of the present invention minimizes the maximum leaf travel distance, the application of the algorithm to dynamic MLC delivery (sweeping algorithm based on Borfeld's work) and direct aperture optimization ("DAO") would possibly lead to faster JMRT plan delivery.
[0053] In the drawings and specification, there have been disclosed a typical preferred embodiment of the invention, and although specific terms are employed, the terms are used in a descriptive sense only and not for purposes of limitation. The invention has been described in considerable detail with specific reference to these illustrated embodiments. It will be apparent, however, that various modifications and changes can be made within the spirit and scope of the invention as described in the foregoing specification and as defined in the appended claims. For example, the discussion primarily focused determining a rotational angle of the multi-leaf collimator for a beam delivery iteration at a single radiation beam delivery angle (gantry angle of rotation for a linear accelerator), hi practice, multiple beam delivery iterations at varying radiation beam delivery angles are required for a single radiation treatment session according to a radiation treatment plan.

Claims

CLAIMS:
1. A computer-implemented method of determining a collimator angle of a multi- leaf collimator having an opening and a plurality of multi-leaf collimator leaf pairs for closing portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments to apply radiation to a tumor target, the method comprising the steps of: calculating an initial radiation beam arrangement according to a desired prescription; and changing the radiation beam arrangement by incorporating a first cost function to determine the collimator angle of the multi-leaf collimator, the first cost function including both a second cost function to enhance delivery efficiency by reducing a number of radiation beam segments and reducing a number of radiation beam monitor units required for delivery of the desired prescription and a third cost function to enhance conformity of the radiation beam arrangement to a target shape.
2. A method as defined in claim 1, wherein the first cost function is obtained by performing the steps of: determining for each one of a plurality of discrete collimator angles a value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in a beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator, a view from the perspective of the opening in the multi-leaf collimator along an axis of the radiation beam defining the beams eye view of the multi-leaf collimator; determining for each one of the plurality of discrete collimator angles a value of a maximum effective length for a multi-leaf collimator leaf pair of the plurality of multi-leaf collimator leaf pairs having the maximum effective length; determining a sum of the value of the area difference and the value of the maximum effective length for each of the plurality of discrete collimator angles; and determining a minimum sum value for the sum of the value of the area difference and the value of the maximum effective length for a collinear angle of the plurality of collimator angles having the minimum sum value.
3. A method as defined in claim 2, further comprising the steps of: selecting a first weight value for the maximum effective length and a second weight value for the area difference, selection criteria including a type of radiation delivery system carrying the multi-leaf collimator and a size and shape of the target; and applying the first weight value to the maximum effective length and the second weight value to the area difference prior to determining the minimum sum value.
4. A method as defined in claim 1, further comprising the step of: rejecting the change in the radiation beam arrangement if the change of the radiation beam arrangement significantly leads to a lesser correspondence to the desired prescription and accepting the change of the radiation beam arrangement if the change of the radiation beam arrangement both leads to more radiation delivery efficiency and does not lead to significantly less correspondence to the desired prescription.
5. A method as defined in claim 1, wherein the first cost function is obtained by the steps of: determining for each one of a plurality of discrete collimator angles a weighted value of an area difference between an area of the opening in the multi- leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in a beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator, according to the formula: Bσ(θ) where σ(θ) is the third cost function describing the area difference between what an multi-leaf collimator can define and the target area, B is a weight factor, and 0 is the collimator angle which varies by discrete increments; determining for each one of the plurality of discrete collimator angles a weighted value of a maximum effective length for a multi-leaf collimator leaf pair of the plurality of multi-leaf collimator leaf pairs having the maximum effective length, according to the following formula: A max[4 (0)] where max[4(0)] is the second cost function describing the maximum effective length for a multi-leaf collimator leaf pair of the plurality of multi-leaf collimator leaf pairs having the maximum effective length, A is a weight factor, and 4 is determined according to the following formula: le = (l + ^-—) 4 mt where n is the number of separated target regions in the path of the multi-leaf collimator leaf pair, ,- is the leaf travel distance in the ith isolated target region for the multi-leaf collimator leaf pair, and k is the weight factor to account for multi-isolated regions in the path over which the multi-leaf collimator leaf pair sweeps; determining a sum of the weighted value of the area difference and the weighted value of the maximum effective length for each of the plurality of discrete collimator angles; and determining a minimum sum value for the sum of the value of the area difference and the value of the maximum effective length for a collinear angle of the plurality of collimator angles having the minimum sum value, according to the following formula: /(00)=minμ max[4 (0)] + Bσ(θ)} where θ0, is the optimized collimator angle.
6. A method of determining a collimator angle of a multi-leaf collimator having an opening and a plurality of multi-leaf collimator leaf pairs for closing portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments to apply radiation to a tumor target, the method comprising the steps of: determining a treatment plan according to a desired prescription; determining for each one of a plurality of discrete collimator angles a value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in a beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator; determining for each one of the plurality of discrete collimator angles a value of a maximum effective length for a multi-leaf collimator leaf pair of the plurality of multi-leaf collimator leaf pairs having the maximum effective length; determining a sum of the value of the area difference and the value of the maximum effective length for each of the plurality of discrete collimator angles; determining a minimum sum value for the sum of the value of the area difference and the value of the maximum effective length for the collimator angle of the plurality of collimator angles having the minimum sum value; and selecting for application to the treatment plan prior to treatment plan optimization, the collimator angle having the minimum sum value.
7. A method as defined in claim 6, further comprising the step of: selecting a first weight value for the maximum effective length and a second weight value for the area difference; and applying the first weight value to the maximum effective length and the second weight value to the area difference prior to determining the minimum sum value.
8. A method as defined in claim 7, wherein the step of selecting a first weight and a second weight further comprises the steps of: determining a type of radiation delivery system carrying the multi-leaf collimator; and determining a size and shape of the target.
9. A method as defined in claim 7, wherein the step of selecting a first weight and a second weight further comprises the step of: selecting a preference between delivery efficiency and target conformity by applying separate first and second weight values to the maximum effective length and area difference, respectively.
10. A method of determining a collimator angle of a multi-leaf collimator having an opening and a plurality of multi-leaf collimator leaf pairs for closing portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments to apply radiation to a tumor target, the method comprising the steps of: providing a cost function having a first delivery efficiency portion providing for enhanced radiation delivery efficiency and a second target conformity portion providing for enhanced target conformity; determining a type of radiation delivery system carrying the multi-leaf collimator; determining a size and a shape of the target; selecting a preference between delivery efficiency and target conformity responsive to the determination of the type of radiation delivery system and the size and the shape of the target; determining a value for the cost function at a selected radiation beam delivery angle incorporating the selected preference; and responsive to the value of the cost function, determining the collimator angle.
11. A method as defined in claim 10, wherein the step of selecting a preference includes the step of assigning separate weight values to the first delivery efficiency portion of the cost function and to the second target conformity portion of the cost function.
12. A method as defined in claim 11, wherein the first delivery efficiency portion of the cost function includes a delivery efficiency cost function that determines at each of a plurality of discrete collimator angles a weighted value of a maximum effective length for a multi-leaf collimator leaf pair of the plurality of multi-leaf collimator leaf pairs having the maximum effective length, and wherein the second target conformity portion of the cost function includes a target conformity cost function that determines at each of a plurality of discrete collimator angles a weighted value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator.
13. A computer readable medium that is readable by a computer determining a collimator angle of a multi-leaf collimator having an opening and a plurality of multi-leaf collimator leaf pairs for closing portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments to apply radiation to a tumor target, the computer readable medium comprising a set of instructions that, when executed by the computer, causes the computer to perform the following operations: determine a treatment plan according to a desired prescription; determine for each one of a plurality of discrete collimator angles a value of an area difference between an area of the opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with the target shape in the beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator; determine for each one of the plurality of discrete collimator angles a value of a maximum effective length for a multi-leaf collimator leaf pair of the plurality of multi-leaf collimator leaf pairs having the maximum effective length; determine a sum of the value of the area difference and the value of the maximum effective length for each of the plurality of discrete collimator angles; determine a minimum sum value for the sum of the value of the area difference and the value of the maximum effective length for a collimator angle of the plurality of collimator angles having the minimum sum value; and select for application to the treatment plan prior to treatment plan optimization, the collimator angle having the minimum sum value.
14. A computer readable medium according to claim 13, further comprising the following set of instructions: receive from a user a first weight value for the maximum effective length and a second weight value for the area difference; and apply the first weight value to the maximum effective length and the second weight value to the area difference prior to determining the minimum sum value.
15. A computer readable medium according to claim 14, further comprising the following set of instructions: determine a type of radiation delivery system carrying the multi-leaf collimator; and determine a size and shape of the target.
16. A computer readable medium according to claim 14, further comprising the following instruction: select a preference between delivery efficiency and target conformity by applying separate user defined first and second weight values to the maximum effective length and area difference, respectively.
17. An apparatus for use in conformal radiation therapy of a target tumor, the apparatus comprising: a multi-leaf collimator having a plurality of selectable discrete collimator angles, an opening to pass a radiation beam, and a plurality of multi-leaf collimator leaf pairs to close portions of the opening to form a radiation beam arrangement having a plurality of radiation beam segments; and a computer in communication with the multi-leaf collimator to form the radiation beam arrangement incorporating a cost function to determine a collimator angle of the multi-leaf collimator to thereby enhance the radiation beam arrangement, the cost function including both parameters to enhance conformity of the radiation beam arrangement to a shape of the target, and parameters to enhance delivery efficiency by reducing a number of segments and reducing a number of monitor units required for delivery of a desired radiation prescription.
18. An apparatus as defined in claim 17, wherein the parameters to enhance delivery efficiency include a value of a maximum effective length for a multi-leaf collimator leaf pair of the plurality of multi-leaf collimator leaf pairs having the maximum effective length.
19. An apparatus as defined in claim 18, wherein the parameters to enhance conformity of the radiation beam arrangement include an area difference between an area of an opening in the multi-leaf collimator which the multi-leaf collimator can define when approaching correspondence with a target shape in a beams eye view of the multi-leaf collimator and an area of the target shape in the same beams eye view of the multi-leaf collimator, a view from the perspective of the opening in the multi-leaf collimator along an axis of the radiation beam defining the beams eye view of the multi-leaf collimator.
20. An apparatus as defined in claim 19, wherein the cost function provides a minimum sum value for the sum of the value of the area difference and the value of the maximum effective length for the collimator angle of the plurality of collimator angles having the minimum sum value.
21. An apparatus as defined in claim 20, further comprising: means for selecting a first weight value for the maximum effective length and a second weight value for the area difference; and means for applying the first weight value to the maximum effective length and the second weight value to the area difference prior to determining the minimum sum value.
PCT/US2004/025922 2003-08-11 2004-08-11 Method and aparatus for optimization of collimator angles in intensity modulated radiation therapy treatment WO2005018742A1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US49422203P 2003-08-11 2003-08-11
US60/494,222 2003-08-11
US10/915,968 US7015490B2 (en) 2003-08-11 2004-08-11 Method and apparatus for optimization of collimator angles in intensity modulated radiation therapy treatment
US10/915,968 2004-08-11

Publications (1)

Publication Number Publication Date
WO2005018742A1 true WO2005018742A1 (en) 2005-03-03

Family

ID=34221355

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/025922 WO2005018742A1 (en) 2003-08-11 2004-08-11 Method and aparatus for optimization of collimator angles in intensity modulated radiation therapy treatment

Country Status (2)

Country Link
US (1) US7015490B2 (en)
WO (1) WO2005018742A1 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3266501A1 (en) * 2016-07-06 2018-01-10 Shenyang Neusoft Medical Systems Co., Ltd. Controlling movement of carriage of multi-leaf collimator
WO2018050886A1 (en) * 2016-09-19 2018-03-22 Varian Medical Systems International Ag Optimization of radiation treatment plans for optimal treatment time in external-beam radiation treatments
WO2018187903A1 (en) * 2017-04-10 2018-10-18 西安大医数码技术有限公司 Multi-leaf collimator control method and system
WO2019185449A1 (en) * 2018-03-30 2019-10-03 Varian Medical Systems International Ag Treating a treatment volume with therapeutic radiation using a multi-leaf collimation system
US10646189B2 (en) 2016-08-08 2020-05-12 Shanghai Neusoft Medical Technology Co., Ltd. Controlling motion position of multi-leaf collimator

Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003076003A2 (en) 2002-03-06 2003-09-18 Tomotherapy Incorporated Method for modification of radiotherapy treatment delivery
GB2418828B (en) * 2004-09-30 2008-07-09 Elekta Ab Anti reflective stepped profile for surfaces of radiotherapeutic apparatus
US7957507B2 (en) 2005-02-28 2011-06-07 Cadman Patrick F Method and apparatus for modulating a radiation beam
GB2424163A (en) * 2005-03-10 2006-09-13 Elekta Ab Radiotherapeutic apparatus utilising helical motion of the source relative to the patient
US8232535B2 (en) 2005-05-10 2012-07-31 Tomotherapy Incorporated System and method of treating a patient with radiation therapy
EP1907984A4 (en) * 2005-07-22 2009-10-21 Tomotherapy Inc Method and system for processing data relating to a radiation therapy treatment plan
EP1907981A4 (en) * 2005-07-22 2009-10-21 Tomotherapy Inc Method and system for evaluating delivered dose
US7839972B2 (en) * 2005-07-22 2010-11-23 Tomotherapy Incorporated System and method of evaluating dose delivered by a radiation therapy system
WO2007014109A2 (en) * 2005-07-22 2007-02-01 Tomotherapy Incorporated System and method of remotely directing radiation therapy treatment
AU2006272730A1 (en) * 2005-07-22 2007-02-01 Tomotherapy Incorporated Method of and system for predicting dose delivery
WO2007014106A2 (en) 2005-07-22 2007-02-01 Tomotherapy Incorporated System and method of delivering radiation therapy to a moving region of interest
US8442287B2 (en) 2005-07-22 2013-05-14 Tomotherapy Incorporated Method and system for evaluating quality assurance criteria in delivery of a treatment plan
EP1907065B1 (en) * 2005-07-22 2012-11-07 TomoTherapy, Inc. Method and system for adapting a radiation therapy treatment plan based on a biological model
ATE507879T1 (en) * 2005-07-22 2011-05-15 Tomotherapy Inc SYSTEM FOR ADMINISTERING RADIATION THERAPY TO A MOVING TARGET AREA
JP2009502255A (en) * 2005-07-22 2009-01-29 トモセラピー・インコーポレーテッド Method and system for assessing quality assurance criteria in the delivery of treatment plans
WO2007014092A2 (en) * 2005-07-22 2007-02-01 Tomotherapy Incorporated Method of placing constraints on a deformation map and system for implementing same
KR20080044250A (en) * 2005-07-23 2008-05-20 토모테라피 인코포레이티드 Radiation therapy imaging and delivery utilizing coordinated motion of gantry and couch
US7469035B2 (en) * 2006-12-11 2008-12-23 The Board Of Trustees Of The Leland Stanford Junior University Method to track three-dimensional target motion with a dynamical multi-leaf collimator
EP2319002A2 (en) * 2008-08-28 2011-05-11 Tomotherapy Incorporated System and method of calculating dose uncertainty
US10086215B2 (en) * 2011-05-17 2018-10-02 Varian Medical Systems International Ag Method and apparatus pertaining to treatment plans for dynamic radiation-treatment platforms
US8615068B2 (en) * 2011-09-23 2013-12-24 Wisconsin Alumni Research Foundation System and method for intensity modulated arc therapy treatment planning
DE102011087590B3 (en) 2011-12-01 2013-06-06 Siemens Aktiengesellschaft Contour collimator with an X-ray impermeable liquid and associated method
DE102012220750B4 (en) 2012-02-08 2015-06-03 Siemens Aktiengesellschaft Contour collimator with a magnetic, X-ray absorbing liquid and associated method
DE102012201856B4 (en) 2012-02-08 2015-04-02 Siemens Aktiengesellschaft Contour collimator and adaptive filter with electroactive polymer elements and associated method
US9144691B2 (en) * 2012-10-22 2015-09-29 Moshe Ein-Gal Optimizing intensity maps for plural orientations using segmented radiation fields
US9443633B2 (en) 2013-02-26 2016-09-13 Accuray Incorporated Electromagnetically actuated multi-leaf collimator
US10398911B2 (en) * 2015-09-25 2019-09-03 Varian Medical Systems Internationl AG Method and apparatus for using a multi-layer multi-leaf collimation system
US10729920B2 (en) * 2015-10-02 2020-08-04 Varian Medical Systems International Ag Systems and methods for quantifying radiation beam conformity
CN108697905B (en) * 2016-03-09 2021-04-06 皇家飞利浦有限公司 Radiotherapy planning apparatus, method and storage medium
WO2017156316A1 (en) 2016-03-09 2017-09-14 Reflexion Medical, Inc. Fluence map generation methods for radiotherapy
EP3630286A4 (en) 2017-05-30 2021-03-03 RefleXion Medical, Inc. Methods for real-time image guided radiation therapy
EP3641884B8 (en) 2017-06-22 2024-01-03 RefleXion Medical, Inc. Methods for calculating bounded dose-volume histograms (dvh) for evaluating a treatment plan
EP3453427A1 (en) * 2017-09-12 2019-03-13 RaySearch Laboratories AB Evaluation of arcs for a radiation treatment plan
JP6918388B2 (en) 2017-09-22 2021-08-11 リフレクション メディカル, インコーポレイテッド Systems and methods for shuttle mode radiation delivery
WO2019160958A1 (en) 2018-02-13 2019-08-22 Reflexion Medical, Inc. Beam station treatment planning and radiation delivery methods
CN109513119B (en) * 2018-11-12 2020-07-17 武汉大学 Volume rotation intensity modulation radiotherapy plan collimator angle optimization method
CN112043976B (en) * 2020-09-28 2022-11-25 上海联影医疗科技股份有限公司 Radiotherapy plan adjustment system and device

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5818902A (en) * 1996-03-01 1998-10-06 Elekta Ab Intensity modulated arc therapy with dynamic multi-leaf collimation
US20030086530A1 (en) * 2001-09-25 2003-05-08 Karl Otto Methods and apparatus for planning and delivering intensity modulated radiation fields with a rotating multileaf collimator

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4672212A (en) * 1985-02-28 1987-06-09 Instrument Ab Scanditronax Multi leaf collimator
US5596619A (en) * 1992-08-21 1997-01-21 Nomos Corporation Method and apparatus for conformal radiation therapy
US6393096B1 (en) * 1998-05-27 2002-05-21 Nomos Corporation Planning method and apparatus for radiation dosimetry
US6853705B2 (en) * 2003-03-28 2005-02-08 The University Of North Carolina At Chapel Hill Residual map segmentation method for multi-leaf collimator-intensity modulated radiotherapy
EA010207B1 (en) * 2003-10-07 2008-06-30 Номос Корпорейшн Planning system, method and apparatus for conformal radiation therapy

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5818902A (en) * 1996-03-01 1998-10-06 Elekta Ab Intensity modulated arc therapy with dynamic multi-leaf collimation
US20030086530A1 (en) * 2001-09-25 2003-05-08 Karl Otto Methods and apparatus for planning and delivering intensity modulated radiation fields with a rotating multileaf collimator

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BEAVIS A W ET AL: "Optimisation of MLC orientation to improve accuracy in the static field delivery of IMRT", PROCEEDINGS OF THE 22ND ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (CAT. NO.00CH37143) IEEE PISCATAWAY, NJ, USA, vol. 4, July 2000 (2000-07-01), pages 3086 - 3089 vol., XP002308750, ISBN: 0-7803-6465-1 *
DU M N ET AL: "A multileaf collimator field prescription preparation system for conventional radiotherapy", INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS UK, vol. 32, no. 2, 1995, pages 513 - 520, XP002308749, ISSN: 0360-3016 *
FRAZIER A ET AL: "Dosimetric evaluation of the conformation of the multileaf collimator to irregularly shaped fields", INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS ELSEVIER UK, vol. 33, no. 5, 1995, pages 1229 - 1238, XP002308751, ISSN: 0360-3016 *
SAMUELSSON A ET AL: "Intensity modulated radiotherapy treatment planning for dynamic multileaf collimator delivery: Influence of different parameters on dose distributions", RADIOTHERAPY AND ONCOLOGY ELSEVIER IRELAND, vol. 66, no. 1, January 2003 (2003-01-01), pages 19 - 28, XP002308752, ISSN: 0167-8140 *
SHEPARD D M ET AL: "Direct aperture optimization: A turnkey solution for step-and-shoot IMRT", MEDICAL PHYSICS, AMERICAN INSTITUTE OF PHYSICS. NEW YORK, US, vol. 29, no. 6, June 2002 (2002-06-01), pages 1007 - 1018, XP012011807, ISSN: 0094-2405 *
WANG D ET AL: "A new algorithm for determining collimator angles that favor efficiency in MLC based IMRT delivery", MEDICAL PHYSICS AIP FOR AMERICAN ASSOC. PHYS. MED USA, vol. 31, no. 5, 23 April 2004 (2004-04-23), pages 1249 - 1253, XP002308753, ISSN: 0094-2405 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3266501A1 (en) * 2016-07-06 2018-01-10 Shenyang Neusoft Medical Systems Co., Ltd. Controlling movement of carriage of multi-leaf collimator
US10128014B2 (en) 2016-07-06 2018-11-13 Shenyang Neusoft Medical Systems Co., Ltd. Controlling movement of carriage of multi-leaf collimator
US10646189B2 (en) 2016-08-08 2020-05-12 Shanghai Neusoft Medical Technology Co., Ltd. Controlling motion position of multi-leaf collimator
WO2018050886A1 (en) * 2016-09-19 2018-03-22 Varian Medical Systems International Ag Optimization of radiation treatment plans for optimal treatment time in external-beam radiation treatments
US10307615B2 (en) 2016-09-19 2019-06-04 Varian Medical Systems International Ag Optimization of radiation treatment plans for optimal treatment time in external-beam radiation treatments
WO2018187903A1 (en) * 2017-04-10 2018-10-18 西安大医数码技术有限公司 Multi-leaf collimator control method and system
US11077321B2 (en) 2017-04-10 2021-08-03 Our United Corporation Method and system of controlling multi-leaf collimator
WO2019185449A1 (en) * 2018-03-30 2019-10-03 Varian Medical Systems International Ag Treating a treatment volume with therapeutic radiation using a multi-leaf collimation system
US11869680B2 (en) 2018-03-30 2024-01-09 Varian Medical Systems International Ag Treating a treatment volume with therapeutic radiation using a multi-leaf collimation system

Also Published As

Publication number Publication date
US20050123098A1 (en) 2005-06-09
US7015490B2 (en) 2006-03-21

Similar Documents

Publication Publication Date Title
US7015490B2 (en) Method and apparatus for optimization of collimator angles in intensity modulated radiation therapy treatment
US11673003B2 (en) Dose aspects of radiation therapy planning and treatment
KR101512994B1 (en) An apparatus for planning a treatment and a method used in the same apparatus
US20230381537A1 (en) Geometric aspects of radiation therapy planning and treatment
Djajaputra et al. Algorithm and performance of a clinical IMRT beam-angle optimization system
US11865364B2 (en) Flash therapy treatment planning and oncology information system having dose rate prescription and dose rate mapping
US7162008B2 (en) Method for the planning and delivery of radiation therapy
US7734010B2 (en) Method and apparatus for planning and delivering radiation treatment
US7801270B2 (en) Treatment plan optimization method for radiation therapy
US6038283A (en) Planning method and apparatus for radiation dosimetry
US7180980B2 (en) Method for intensity modulated radiation treatment using independent collimator jaws
US5513238A (en) Automatic planning for radiation dosimetry
EP2200698B1 (en) Method and apparatus for intensity modulated arc therapy sequencing and optimization
US20030212325A1 (en) Method for determining a dose distribution in radiation therapy
US6661872B2 (en) Intensity modulated radiation therapy planning system
Diot et al. Biological‐based optimization and volumetric modulated arc therapy delivery for stereotactic body radiation therapy
Li et al. Genetic algorithm based deliverable segments optimization for static intensity-modulated radiotherapy
Meyer et al. Automatic selection of non-coplanar beam directions for three-dimensional conformal radiotherapy
Battinelli et al. Collimator angle optimization for multiple brain metastases in dynamic conformal arc treatment planning
Anker et al. Evaluation of fluence‐smoothing feature for three IMRT planning systems
Wang et al. A new algorithm for determining collimator angles that favor efficiency in MLC based IMRT delivery
Stapper et al. Automated isocenter optimization approach for treatment planning for gyroscopic radiosurgery
WO2023213877A1 (en) System and method for automated radiotherapy treatment planning

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase