IP Library Granted Patent US 12,390,662
Granted Patent B2
US 12,390,662 · App. 16/838,940 · Granted Aug 19, 2025

System and method for proton therapy treatment planning with proton energy and spot optimization

Inventors: Timo Koponen (Espoo, FI); Perttu Niemela (Espoo, FI)
Assignee: SIEMENS HEALTHINEERS INTERNATIONAL AG
A61N5/1031A61N5/1081G16H20/40A61N2005/1087
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Quick Facts
Patent No.
US 12,390,662
App. No.
16/838,940
Granted
Aug 19, 2025
Kind
B2
Abstract

Embodiments of the present invention disclose methods and systems for proton therapy planning that includes proton energy and spot optimization that discretizes layers and spots using an optimization algorithm to produce an optimal distribution of layer energies and spots with a relatively smooth dose distribution. The treatment planning algorithms disclosed herein can freely choose the number of spots and the energy levels of the spots. In this way, each spot can be treated as its own layer and is not constrained by the requirements of other spots/layers. Thereafter, the spots defined by the algorithm can be sorted in a list according to energy levels/depth, and the spots can be grouped into blocks according to intensity and location. The blocks can be assigned energy levels based on the corresponding spots, such as an average of all the spots associated with the block. The blocks then are used as the energy layers applied by the proton therapy treatment system.

Claims (29)

1. A system for proton therapy treatment, the system comprising:

a gantry including a nozzle configured to emit a controllable proton beam;

a proton therapy treatment system configured to automatically control the gantry according to a treatment plan; and

a treatment planning system including

a memory, and

a processor configured to

receive treatment planning parameters,

determine a quantity of spots, among a plurality of spots,

according to the treatment planning parameters,

determine an energy for each spot, among the plurality of spots, according to the treatment planning parameters,

calculate intensities for the plurality of spots according to the energy for each spot, among the plurality of spots,

discretize the plurality of spots into a plurality of blocks according to locations of the plurality of spots and intensities of the plurality of spots to generate the treatment plan, wherein

the treatment plan includes the plurality of blocks, and

each block, among the plurality of blocks, represents an energy layer, among a number of energy layers, applied by the controllable proton beam, and

output the treatment plan to the proton therapy treatment system to perform the proton therapy treatment; wherein

the proton therapy treatment system is configured to automatically control at least one of an intensity, energy, size or shape of the controllable proton beam emitted by the nozzle according to the treatment plan.

2. The system as described in claim 1 , wherein the system is configured to treat a patient using the gantry according to the treatment plan.

3. The system as described in claim 1 , wherein the processor is configured to iteratively repeat the discretizing of the plurality of spots until a clinical goal is achieved.

4. The system as described in claim 1 , wherein the processor is configured to

determine a plurality of angles for performing the proton therapy treatment, and

determine the quantity of spots and the energy for each spot according to the treatment planning parameters and the plurality of angles.

5. The system as described in claim 1 , wherein the processor is configured to

receive the number of energy layers as user input, and

determine the quantity of spots and the energy for each spot according to the treatment planning parameters and the number of energy layers.

6. The system as described in claim 1 , wherein the processor is configured to sort the plurality of spots according to depth before discretizing the plurality of spots.

7. The system as described in claim 1 , wherein the processor is configured to sort the plurality of spots according to the energy of each spot before discretizing the plurality of spots.

8. The system as described in claim 1 , wherein the energy layers are spaced apart from one another by a fixed spacing.

9. The system as described in claim 1 , wherein the energy layers have a fixed total intensity.

10. The system of claim 1 , wherein each energy layer, among the number of energy layers, has the same intensity as other energy layers among the number of energy layers.

Assignments (2)
CHANGE OF NAME Recorded Sep 11, 2024
From: VARIAN MEDICAL SYSTEMS INTERNATIONAL AG
To: SIEMENS HEALTHINEERS INTERNATIONAL AG
Reel/Frame 068946/0110 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 9, 2020
From: NIEMELA, PERTTU; KOPONEN, TIMO
To: VARIAN MEDICAL SYSTEMS INTERNATIONAL AG
Reel/Frame 054312/0962 →
Continuity (1)
Related Publication 20210308485A1 · Oct 7, 2021
References Cited (301)
US 4163901A · Azam · 1979 [cited by applicant]
US 4914681A · Klingenbeck et al. · 1990 [cited by applicant]
US 5153900A · Nomikos et al. · 1992 [cited by applicant]
US 5267294A · Kuroda · 1993 [cited by applicant]
US 5550378A · Skillicorn et al. · 1996 [cited by applicant]
US 5610967A · Moorman et al. · 1997 [cited by applicant]
US 5625663A · Swerdloff et al. · 1997 [cited by applicant]
US 5682412A · Skillicom et al. · 1997 [cited by applicant]
US 5757885A · Yao et al. · 1998 [cited by applicant]
US 6198802B1 · Elliott et al. · 2001 [cited by applicant]
US 6222544B1 · Tarr et al. · 2001 [cited by applicant]
US 6234671B1 · Solomon et al. · 2001 [cited by applicant]
US 6260005B1 · Yang et al. · 2001 [cited by applicant]
US 6379380B1 · Satz · 2002 [cited by applicant]
US 6411675B1 · Llacer · 2002 [cited by applicant]
US 6445766B1 · Whitham · 2002 [cited by applicant]
US 6504899B2 · Pugachev et al. · 2003 [cited by applicant]
US 6580940B2 · Gutman · 2003 [cited by applicant]
US 6993112B2 · Hesse · 2006 [cited by applicant]
US 7268358B2 · Ma et al. · 2007 [cited by applicant]
US 7453983B2 · Schildkraut et al. · 2008 [cited by applicant]
US 7515681B2 · Ebstein · 2009 [cited by applicant]
US 7522706B2 · Lu et al. · 2009 [cited by applicant]
US 7560715B2 · Pedroni · 2009 [cited by applicant]
US 7590219B2 · Maurer, Jr. et al. · 2009 [cited by applicant]
US 7616735B2 · Maciunas et al. · 2009 [cited by applicant]
US 7623623B2 · Raanes et al. · 2009 [cited by applicant]
US 7778691B2 · Zhang et al. · 2010 [cited by applicant]
US 7807982B2 · Nishiuchi et al. · 2010 [cited by applicant]
US 7831289B2 · Riker et al. · 2010 [cited by applicant]
US 7835492B1 · Sahadevan · 2010 [cited by applicant]
US 7907699B2 · Long et al. · 2011 [cited by applicant]
US 8284898B2 · Ho et al. · 2012 [cited by applicant]
US 8306184B2 · Chang et al. · 2012 [cited by applicant]
US 8401148B2 · Lu et al. · 2013 [cited by applicant]
US 8406844B2 · Ruchala et al. · 2013 [cited by applicant]
US 8559596B2 · Thomson et al. · 2013 [cited by applicant]
US 8600003B2 · Zhou et al. · 2013 [cited by applicant]
US 8613694B2 · Walsh · 2013 [cited by applicant]
US 8636636B2 · Shukla et al. · 2014 [cited by applicant]
US 8644571B1 · Schulte et al. · 2014 [cited by applicant]
US 8716663B2 · Brusasco et al. · 2014 [cited by applicant]
US 8836332B2 · Shvartsman et al. · 2014 [cited by applicant]
US 8847179B2 · Fujitaka et al. · 2014 [cited by applicant]
US 8903471B2 · Heid · 2014 [cited by applicant]
US 8917813B2 · Maurer, Jr. · 2014 [cited by applicant]
US 8948341B2 · Beckman · 2015 [cited by applicant]
US 8958864B2 · Amies et al. · 2015 [cited by applicant]
US 8983573B2 · Carlone et al. · 2015 [cited by applicant]
US 8986186B2 · Zhang et al. · 2015 [cited by applicant]
US 8992404B2 · Graf et al. · 2015 [cited by applicant]
US 8995608B2 · Zhou et al. · 2015 [cited by applicant]
US 9018603B2 · Loo et al. · 2015 [cited by applicant]
US 9033859B2 · Fieres et al. · 2015 [cited by applicant]
US 9079027B2 · Agano et al. · 2015 [cited by applicant]
US 9149656B2 · Tanabe · 2015 [cited by applicant]
US 9155908B2 · Meltsner et al. · 2015 [cited by applicant]
US 9233260B2 · Slatkin et al. · 2016 [cited by applicant]
US 9258876B2 · Cheung et al. · 2016 [cited by applicant]
US 9283406B2 · Prieels · 2016 [cited by applicant]
US 9308391B2 · Liu et al. · 2016 [cited by applicant]
US 9330879B2 · Lewellen et al. · 2016 [cited by applicant]
US 9333374B2 · Iwata · 2016 [cited by applicant]
US 9468777B2 · Fallone et al. · 2016 [cited by applicant]
US 9517358B2 · Velthuis et al. · 2016 [cited by applicant]
US 9526918B2 · Kruip · 2016 [cited by applicant]
US 9545444B2 · Strober et al. · 2017 [cited by applicant]
US 9583302B2 · Figueroa Saavedra et al. · 2017 [cited by applicant]
US 9636381B2 · Basile · 2017 [cited by applicant]
US 9636525B1 · Sahadevan · 2017 [cited by applicant]
US 9649298B2 · Djonov et al. · 2017 [cited by applicant]
US 9656098B2 · Goer · 2017 [cited by applicant]
US 9694204B2 · Hardemark · 2017 [cited by applicant]
US 9776017B2 · Flynn et al. · 2017 [cited by applicant]
US 9786054B2 · Taguchi et al. · 2017 [cited by applicant]
US 9786093B2 · Svensson · 2017 [cited by applicant]
US 9786465B2 · Li et al. · 2017 [cited by applicant]
US 9795806B2 · Matsuzaki et al. · 2017 [cited by applicant]
US 9801594B2 · Boyd et al. · 2017 [cited by applicant]
US 9844358B2 · Wiggers et al. · 2017 [cited by applicant]
US 9854662B2 · Mishin · 2017 [cited by applicant]
US 9884206B2 · Schulte et al. · 2018 [cited by applicant]
US 9931522B2 · Bharadwaj et al. · 2018 [cited by applicant]
US 9962562B2 · Fahrig et al. · 2018 [cited by applicant]
US 9974977B2 · Lachaine et al. · 2018 [cited by applicant]
US 9987502B1 · Gattiker et al. · 2018 [cited by applicant]
US 10007961B2 · Grudzinski et al. · 2018 [cited by applicant]
US 10022564B2 · Thieme et al. · 2018 [cited by applicant]
US 10071264B2 · Liger · 2018 [cited by applicant]
US 10080912B2 · Kwak et al. · 2018 [cited by applicant]
US 10092774B1 · Vanderstraten et al. · 2018 [cited by applicant]
US 10183179B1 · Smith et al. · 2019 [cited by applicant]
US 10188875B2 · Kwak et al. · 2019 [cited by applicant]
US 10206871B2 · Lin et al. · 2019 [cited by applicant]
US 10212800B2 · Agustsson et al. · 2019 [cited by applicant]
US 10232193B2 · Iseki · 2019 [cited by applicant]
US 10258810B2 · Zwart et al. · 2019 [cited by applicant]
US 10272264B2 · Ollila et al. · 2019 [cited by applicant]
US 10279196B2 · West et al. · 2019 [cited by applicant]
US 10293184B2 · Pishdad et al. · 2019 [cited by applicant]
US 10307614B2 · Schnarr · 2019 [cited by applicant]
US 10307615B2 · Ollila et al. · 2019 [cited by applicant]
US 10315047B2 · Glimelius et al. · 2019 [cited by applicant]
US 10413755B1 · Sahadevan · 2019 [cited by applicant]
US 10449389B2 · Ollila et al. · 2019 [cited by applicant]
US 10485988B2 · Kuusela et al. · 2019 [cited by applicant]
US 10525285B1 · Friedman · 2020 [cited by applicant]
US 10549117B2 · Vanderstraten et al. · 2020 [cited by applicant]
US 10603514B2 · Grittani et al. · 2020 [cited by applicant]
US 10609806B2 · Roecken et al. · 2020 [cited by applicant]
US 10636609B1 · Bertsche et al. · 2020 [cited by applicant]
US 10660588B2 · Boyd et al. · 2020 [cited by applicant]
US 10661100B2 · Shen · 2020 [cited by applicant]
US 10682528B2 · Ansorge et al. · 2020 [cited by applicant]
US 10702716B2 · Heese · 2020 [cited by applicant]
US 10758746B2 · Kwak et al. · 2020 [cited by applicant]
US 10870018B2 · Bartkoski et al. · 2020 [cited by applicant]
US 20040227104A1 · Matsuda · 2004 [cited by examiner]
US 20070287878A1 · Fantini et al. · 2007 [cited by applicant]
US 20080023644A1 · Pedroni · 2008 [cited by applicant]
US 20090063110A1 · Failla et al. · 2009 [cited by applicant]
US 20090287467A1 · Sparks et al. · 2009 [cited by applicant]
US 20100119032A1 · Yan et al. · 2010 [cited by applicant]
US 20100177870A1 · Nord et al. · 2010 [cited by applicant]
US 20100178245A1 · Arnsdorf et al. · 2010 [cited by applicant]
US 20100260317A1 · Chang et al. · 2010 [cited by applicant]
US 20100327188A1 · Bert et al. · 2010 [cited by applicant]
US 20110006224A1 · Maltz et al. · 2011 [cited by applicant]
US 20110091015A1 · Yu et al. · 2011 [cited by applicant]
US 20110135058A1 · Sgouros et al. · 2011 [cited by applicant]
US 20120076271A1 · Yan et al. · 2012 [cited by applicant]
US 20120157746A1 · Meltsner et al. · 2012 [cited by applicant]
US 20120171745A1 · Itoh · 2012 [cited by applicant]
US 20120197058A1 · Shukla et al. · 2012 [cited by applicant]
US 20130116929A1 · Carlton et al. · 2013 [cited by applicant]
US 20130150922A1 · Butson et al. · 2013 [cited by applicant]
US 20130177641A1 · Ghoroghchian · 2013 [cited by applicant]
US 20130231516A1 · Loo et al. · 2013 [cited by applicant]
US 20130267756A1 · Totake · 2013 [cited by examiner]
US 20140177807A1 · Lewellen et al. · 2014 [cited by applicant]
US 20140185776A1 · Li et al. · 2014 [cited by applicant]
US 20140206926A1 · van der Laarse · 2014 [cited by applicant]
US 20140275706A1 · Dean et al. · 2014 [cited by applicant]
US 20140369476A1 · Harding · 2014 [cited by applicant]
US 20150011817A1 · Feng · 2015 [cited by applicant]
US 20150202464A1 · Brand et al. · 2015 [cited by applicant]
US 20150265855A1 · Tachikawa · 2015 [cited by examiner]
US 20150306423A1 · Bharat et al. · 2015 [cited by applicant]
US 20160279444A1 · Schlosser · 2016 [cited by applicant]
US 20160310764A1 · Bharadwaj et al. · 2016 [cited by applicant]
US 20170189721A1 · Sumanaweera et al. · 2017 [cited by applicant]
US 20170203129A1 · Dessy · 2017 [cited by applicant]
US 20170216622A1 · Fujitaka et al. · 2017 [cited by applicant]
US 20170281973A1 · Allen et al. · 2017 [cited by applicant]
US 20180021594A1 · Papp et al. · 2018 [cited by applicant]
US 20180043183A1 · Sheng et al. · 2018 [cited by applicant]
US 20180056090A1 · Jordan et al. · 2018 [cited by applicant]
US 20180099154A1 · Prieels · 2018 [cited by applicant]
US 20180099155A1 · Prieels et al. · 2018 [cited by applicant]
US 20180099159A1 · Forton et al. · 2018 [cited by applicant]
US 20180154183A1 · Sahadevan · 2018 [cited by applicant]
US 20180197303A1 · Jordan et al. · 2018 [cited by applicant]
US 20180207425A1 · Carlton et al. · 2018 [cited by applicant]
US 20180236268A1 · Zwart et al. · 2018 [cited by applicant]
US 20190022407A1 · Abel et al. · 2019 [cited by applicant]
US 20190022422A1 · Trail et al. · 2019 [cited by applicant]
US 20190054315A1 · Isola et al. · 2019 [cited by applicant]
US 20190070435A1 · Joe Anto et al. · 2019 [cited by applicant]
US 20190168027A1 · Smith et al. · 2019 [cited by applicant]
US 20190255361A1 · Mansfield · 2019 [cited by applicant]
US 20190299027A1 · Fujii et al. · 2019 [cited by applicant]
US 20190299029A1 · Inoue · 2019 [cited by applicant]
US 20190351259A1 · Lee et al. · 2019 [cited by applicant]
US 20200001118A1 · Snider, III et al. · 2020 [cited by applicant]
US 20200022248A1 · Yi et al. · 2020 [cited by applicant]
US 20200030633A1 · Van Heteren et al. · 2020 [cited by applicant]
US 20200035438A1 · Star-Lack et al. · 2020 [cited by applicant]
US 20200069818A1 · Jaskula-Ranga et al. · 2020 [cited by applicant]
US 20200164224A1 · Vanderstraten et al. · 2020 [cited by applicant]
US 20200178890A1 · Otto · 2020 [cited by applicant]
US 20200197730A1 · Safavi-Naeini et al. · 2020 [cited by applicant]
US 20200254279A1 · Ohishi · 2020 [cited by applicant]
US 20200269068A1 · Abel et al. · 2020 [cited by applicant]
US 20200276456A1 · Swerdloff · 2020 [cited by applicant]
US 20200282234A1 · Folkerts et al. · 2020 [cited by applicant]
US 20200298025A1 · Cooley, III · 2020 [cited by examiner]
CN 104001270 · 2014 [cited by applicant]
CN 106730407 · 2017 [cited by applicant]
CN 107362464 · 2017 [cited by applicant]
CN 109966662 · 2019 [cited by applicant]
CN 111481840 · 2020 [cited by applicant]
CN 111481841 · 2020 [cited by applicant]
EA 010207 · 2008 [cited by applicant]
EP 0979656 · 2000 [cited by applicant]
EP 2510978 · 2012 [cited by applicant]
EP 3178522 · 2017 [cited by applicant]
EP 3338858 · 2018 [cited by applicant]
EP 3384961 · 2018 [cited by applicant]
EP 3421087 · 2019 [cited by applicant]
EP 3453427 · 2019 [cited by applicant]
EP 3586920 · 2020 [cited by applicant]
JP 2617283 · 1997 [cited by applicant]
JP 2019097969 · 2019 [cited by applicant]
WO 2007017177 · 2007 [cited by applicant]
WO 2010018476 · 2010 [cited by applicant]
WO 2013081218 · 2013 [cited by applicant]
WO 2013133936 · 2013 [cited by applicant]
WO 2014139493 · 2014 [cited by applicant]
WO 2015038832 · 2015 [cited by applicant]
WO 2015102680 · 2015 [cited by applicant]
WO 2016122957 · 2016 [cited by applicant]
WO 2017156316 · 2017 [cited by applicant]
WO 2017156419 · 2017 [cited by applicant]
WO 2017174643 · 2017 [cited by applicant]
WO 2018137772 · 2018 [cited by applicant]
WO 2018152302 · 2018 [cited by applicant]
WO 2019097250 · 2019 [cited by applicant]
WO 2019103983 · 2019 [cited by applicant]
WO 2019164835 · 2019 [cited by applicant]
WO 2019166702 · 2019 [cited by applicant]
WO 2019185378 · 2019 [cited by applicant]
WO 2019222436 · 2019 [cited by applicant]
WO 2020018904 · 2020 [cited by applicant]
WO 2020064832 · 2020 [cited by applicant]
WO 2020107121 · 2020 [cited by applicant]
WO 2020159360 · 2020 [cited by applicant]
M. McManus et al., “The challenge of ionisation chamber dosimetry in ultra-short pulsed high dose-rate Very High Energy Electron beams,” Sci Rep 10, 9089 (2020), published Jun. 3, 2020, https://doi.org/10.1038/s41598-02… [cited by applicant]
Ibrahim Oraiqat et al., “An Ionizing Radiation Acoustic Imaging (iRAI) Technique for Real-Time Dosimetric Measurements for FLASH Radiotherapy,” Medical Physics, vol. 47, Issue 10, Oct. 2020, pp. 5090-5101, First publish… [cited by applicant]
K. Petersson et al., “Dosimetry of ultra high dose rate irradiation for studies on the biological effect induced in normal brain and GBM,” ICTR-PHE 2016, p. S84, Feb. 2016, https://publisher-connector.core.ac.uk/resourc… [cited by applicant]
Susanne Auer et al., “Survival of tumor cells after proton irradiation with ultra-high dose rates,” Radiation Oncology 2011, 6:139, Published Oct. 18, 2011, DOI: https://doi.org/10.1186/1748-717X-6-139. [cited by applicant]
Cynthia E. Keen, “Clinical linear accelerator delivers FLASH radiotherapy,” Physics World, Apr. 23, 2019, IOP Publishing Ltd, https://physicsworld.com/a/clinical-linear-accelerator-delivers-flash-radiotherapy/. [cited by applicant]
Fan et al., “Emission guided radiation therapy for lung and prostate cancers: A feasibility study on a digital patient,” Med Phys. Nov. 2012; 39(11): 7140-7152. Published online Nov. 5, 2012. https://www.ncbi.nlm.nih.go… [cited by applicant]
Favaudon et al., “Ultrahigh dose-rate, “flash” irradiation minimizes the side-effects of radiotherapy,” Cancer / Radiotherapy, vol. 19, Issues 6-7 , Oct. 2015 , pp. 526-531, Available online Aug. 12, 2015, https://doi.o… [cited by applicant]
O. Zlobinskaya et al., “The Effects of Ultra-High Dose Rate Proton Irradiation on Growth Delay in the Treatment of Human Tumor Xenografts in Nude Mice,” Radiation Research, 181(2):177-183. Published Feb. 13, 2014, DOI: … [cited by applicant]
Bjorn Zackrisson, “Biological Effects Of High Energy Radiation And Ultra High Dose Rates,” UMEA University Medical Dissertations, New series No. 315—ISSN 0346-6612, From the Department of Oncology, University of Umea, U… [cited by applicant]
P. Montay-Gruel et al., “Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s,” Radiotherapy and Oncology, vol. 124, Issue 3, Sep. 2017, pp. 365-369, Avai… [cited by applicant]
BW Loo et al., “Delivery of Ultra-Rapid Flash Radiation Therapy and Demonstration of Normal Tissue Sparing After Abdominal Irradiation of Mice,” International Journal of Radiation Oncology, Biology, Physics, vol. 98, Is… [cited by applicant]
Bhanu Prasad Venkatesulu et al., “Ultra high dose rate (35 Gy/sec) radiation does not spare the normal tissue In cardiac and splenic models of lymphopenia and gastrointestinal syndrome,” Sci Rep 9, 17180 (2019), Publish… [cited by applicant]
P. Montay-Gruel et al., “Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species,” PNAS May 28, 2019, vol. 116, No. 22, pp. 10943-10951; first published May 16, 2019, https://do… [cited by applicant]
Peter G. Maxim et al., “FLASH radiotherapy: Newsflash or flash in the pan?”, Medical Physics, 46 (10), Oct. 2019, pp. 4287-4290, American Association of Physicists in Medicine, First published: Jun. 27, 2019, https://do… [cited by applicant]
Andrei Pugachev et al., “Pseudo beam's-eye-view as applied to beam orientation selection in intensity-modulated radiation therapy,” Int. J. Radiation Oncology Biol. Phys., vol. 51, Issue 5, p. 1361-1370, Dec. 1, 2001, D… [cited by applicant]
Xiaodong Zhang et al., “Intensity-Modulated Proton Therapy Reduces the Dose to Normal Tissue Compared With Intensity-Modulated Radiation Therapy or Passive Scattering Proton Therapy and Enables Individualized Radical Ra… [cited by applicant]
A. J. Lomax et al., “Intensity modulated proton therapy: A clinical example,” Medical Physics, vol. 28, Issue 3, Mar. 2001, pp. 317-324, First published: Mar. 9, 2001, https://doi.org/10.1118/1.1350587. [cited by applicant]
Lamberto Widesott et al., “Intensity-Modulated Proton Therapy Versus Helical Tomotherapy in Nasopharynx Cancer: Planning Comparison and NTCP Evaluation,” Int. J. Radiation Oncology Biol. Phys., vol. 72, No. 2, pp. 589-5… [cited by applicant]
Andrei Pugachev et al., “Role of beam orientation optimization in intensity-modulated radiation therapy,” Int. J. Radiation Oncology Biol. Phys., vol. 50, No. 2, pp. 551-560, Jun. 1, 2001, Available online May 10, 2001,… [cited by applicant]
Damien C. Weber et al., “Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview,” Radiat Oncol. 2006; 1: 22. Published online Jul. 20, 2006, doi: 10.1186/1748-717X-1-22. [cited by applicant]
RaySearch Laboratories, “Leading the way in cancer treatment, Annual Report 2013,” RaySearch Laboratories (publ), Stockholm, Sweden, 94 pages, Apr. 2014, https://www.raysearchlabs.com/siteassets/about-overview/media-cen… [cited by applicant]
Fredrik Carlsson, “Utilizing Problem Structure in Optimization of Radiation Therapy,” KTH Engineering Sciences, Doctoral Thesis, Stockholm, Sweden, Apr. 2008, Optimization and Systems Theory, Department of Mathematics, … [cited by applicant]
Chang-Ming Charlie Ma, “Physics and Dosimetric Principles of SRS and SBRT,” Mathews J Cancer Sci. 4(2): 22, 2019, published: Dec. 11, 2019, ISSN: 2474-6797, DOI: https://doi.org/10.30654/MJCS.10022. [cited by applicant]
Alterego-Admin, “Conventional Radiation Therapy May Not Protect Healthy Brain Cells,” International Neuropsychiatric Association—INA, Oct. 10, 2019, https://inawebsite.org/conventional-radiation-therapy-may-not-protect-… [cited by applicant]
Schell Stefan et al., “Advanced treatment planning methods for efficient radiation therapy with laser accelarated proton and ion beams”, Medical Physics, AIP, Melville, NY, US, vol. 37, No. 10, Sep. 20, 2010 (Sep. 20, 2… [cited by applicant]
Aafke Christine Kraan, “Range verification methods in particle therapy: underlying physics and Monte Carlo modeling,” Frontiers in Oncology, Jul. 7, 2015, vol. 5, Article 150, 27 pages, doi: 10.3389/fonc.2015.00150. [cited by applicant]
Wayne D. Newhauser et al., “The physics of proton therapy,” Physics in Medicine & Biology, Mar. 24, 2015, 60 R155-R209, Institute of Physics and Engineering in Medicine, IOP Publishing, doi: 10.1088/0031-9155/60/8/R155. [cited by applicant]
S E McGowan et al., “Treatment planning optimisation in proton therapy,” Br J Radiol, 2013, 86, 20120288, The British Institute of Radiology, 12 pages, DOI: 10.1259.bjr.20120288. [cited by applicant]
Steven Van De Water et al., “Towards FLASH proton therapy: the impact of treatment planning and machine characteristics on achievable dose rates,” Acta Oncologica, Jun. 26, 2019, vol. 58, No. 10, p. 1462-1469, Taylor & … [cited by applicant]
J. Groen, “FLASH optimisation in clinical IMPT treatment planning,” MSc Thesis, Jul. 1, 2020, Erasmus University Medical Center, department of radiotherapy, Delft University of Technology, 72 pages. [cited by applicant]
Muhammad Ramish Ashraf et al., “Dosimetry for FLASH Radiotherapy: A Review of Tools and the Role of Radioluminescence and Cherenkov Emission,” Frontiers in Oncology, Aug. 21, 2020, vol. 8, Article 328, 20 pages, doi: 10… [cited by applicant]
Emil Schuler et al., “Experimental Platform for Ultra-high Dose Rate FLASH Irradiation of Small Animals Using a Clinical Linear Accelerator,” International Journal of Radiation Oncology, Biology, Physics, vol. 97, No. 1… [cited by applicant]
Elette Engels et al., “Toward personalized synchrotron microbeam radiation therapy,” Scientific Reports, 10:8833, Jun. 1, 2020, 13 pages, DOI: https://doi.org/10.1038/s41598-020-65729-z. [cited by applicant]
P-H Mackeprang et al., “Assessing dose rate distributions in VMAT plans” (Accepted Version), Accepted Version: https://boris.unibe.ch/92814/8/dose_rate_project_revised_submit.pdf Published Version: 2016, Physics in medi… [cited by applicant]
Xiaoying Liang et al., “Using Robust Optimization for Skin Flashing in Intensity Modulated Radiation Therapy for Breast Cancer Treatment: A Feasibility Study,” Practical Radiation Oncology, vol. 10, Issue 1, p. 59-69, P… [cited by applicant]
Alexei Trofimov et al., “Optimization of Beam Parameters and Treatment Planning for Intensity Modulated Proton Therapy,” Technology in Cancer Research & Treatment, vol. 2, No. 5, Oct. 2003, p. 437-444, Adenine Press. [cited by applicant]
Vladimir Anferov, “Scan pattern optimization for uniform proton beam scanning,” Medical Physics, vol. 36, Issue 8, Aug. 2009, pp. 3560-3567, First published: Jul. 2, 2009. [cited by applicant]
Ryosuke Kohno et al., “Development of Continuous Line Scanning System Prototype for Proton Beam Therapy,” International Journal of Particle Therapy, Jul. 11, 2017, vol. 3, Issue 4, p. 429-438, DOI: 10.14338/IJPT-16-0001… [cited by applicant]
Wenbo Gu et al., “Integrated Beam Orientation and Scanning-Spot Optimization in Intensity Modulated Proton Therapy for Brain and Unilateral Head and Neck Tumors,” Med Phys. Author manuscript; available in PMC Apr. 1, 20… [cited by applicant]
Paul Morel et al., “Spot weight adaptation for moving target in spot scanning proton therapy,” Frontiers in Oncology, May 28, 2015, vol. 5, Article 119, 7 pages, doi: 10.3389/fonc.2015.00119. [cited by applicant]
Simeon Nill et al., “Inverse planning of intensity modulated proton therapy,” Zeitschrift fur Medizinische Physik, vol. 14, Issue 1, 2004, pp. 35-40, https://doi.org/10.1078/0939-3889-00198. [cited by applicant]
A. Lomax, “Intensity modulation methods for proton radiotherapy,” Physics in Medicine & Biology, Jan. 1999, vol. 44, No. 1, pp. 185-205, doi: 10.1088/0031-9155/44/1/014. [cited by applicant]
M Kramer et al., “Treatment planning for heavy-ion radiotherapy: physical beam model and dose optimization,” Physics in Medicine & Biology, 2000, vol. 45, No. 11, pp. 3299-3317, doi: 10.1088/0031-9155/45/11/313. [cited by applicant]
Harald Paganetti, “Proton Beam Therapy,” Jan. 2017, Physics World Discovery, IOP Publishing Ltd, Bristol, UK, 34 pages, DOI: 10.1088/978-0-7503-1370-4. [cited by applicant]
Shinichi Shimizu et al., “A Proton Beam Therapy System Dedicated to Spot-Scanning Increases Accuracy with Moving Tumors by Real-Time Imaging and Gating and Reduces Equipment Size,” PLoS One, Apr. 18, 2014, vol. 9, Issue… [cited by applicant]
Heng Li et al., “Reducing Dose Uncertainty for Spot-Scanning Proton Beam Therapy of Moving Tumors by Optimizing the Spot Delivery Sequence,” International Journal of Radiation Oncology, Biology, Physics, vol. 93, Issue … [cited by applicant]
Ion Beam Applications SA, “Netherlands Proton Therapy Center Delivers First Clinical Flash Irradiation,” Imaging Technology News, May 2, 2019, Wainscot Media, https://www.itnonline.com/content/netherlands-proton-therapy… [cited by applicant]
R. M. De Kruijff, “FLASH radiotherapy: ultra-high dose rates to spare healthy tissue,” International Journal of Radiation Biology, 2020, vol. 96, No. 4, pp. 419-423, published online: Dec. 19, 2019, https://doi.org/10.1… [cited by applicant]
Mevion Medical Systems, “Focus On The Future: Flash Therapy,” Press Releases, Sep. 16, 2019, https://www.mevion.com/newsroom/press-releases/focus-future-flash-therapy. [cited by applicant]
Joseph D. Wilson et al., “Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?”, Frontiers in Oncology, Jan. 17, 2020, vol. 9, Article 1563, 12 pages, doi: 10.3389/fonc.2019.01563. [cited by applicant]
David P. Gierga, “Is Flash Radiotherapy coming?”, International Organization for Medical Physics, 2020, https://www.iomp.org/iomp-news2-flash-radiotherapy/. [cited by applicant]
Abdullah Muhammad Zakaria et al., “Ultra-High Dose-Rate, Pulsed (FLASH) Radiotherapy with Carbon Ions: Generation of Early, Transient, Highly Oxygenated Conditions in the Tumor Environment,” Radiation Research, Dec. 1, … [cited by applicant]
Yusuke Demizu et al., “Carbon Ion Therapy for Early-Stage Non-Small-Cell Lung Cancer,” BioMed Research International, vol. 2014, Article ID 727962, 9 pages, Hindawi Publishing Corporation, published: Sep. 11, 2014, http… [cited by applicant]
Ivana Dokic et al., “Next generation multi-scale biophysical characterization of high precision cancer particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion beams,” Oncotarget, Aug. 30, 2016, vol.… [cited by applicant]
Aetna Inc., “Proton Beam, Neutron Beam, and Carbon Ion Radiotherapy,” 2020, No. 0270, http://www.aetna.com/cpb/medical/data/200_299/0270.html. [cited by applicant]
Nicholas W. Colangelo et al., “The Importance and Clinical Implications of FLASH Ultra-High Dose-Rate Studies for Proton and Heavy Ion Radiotherapy,” Radiat Res. Author manuscript; available in PMC Jan. 1, 2021. https:/… [cited by applicant]
Vincent Favaudon et al., “Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice,” Science Translational Medicine, Jul. 16, 2014, vol. 6, Issue 245, 245ra93, Am… [cited by applicant]
“FlashRad: Ultra-high dose-rate FLASH radiotherapy to minimize the complications of radiotherapy,” 2014, https://siric.curie.fr/sites/default/files/atoms/files/flashrad.pdf. [cited by applicant]
Tami Freeman, “FLASH radiotherapy: from preclinical promise to the first human treatment,” Physics World, Aug. 6, 2019, IOP Publishing Ltd, https://physicsworld.com/a/flash-radiotherapy-from-preclinical-promise-to-the-f… [cited by applicant]
Intraop Medical, Inc., “IntraOp and Lausanne University Hospital Announce Collaboration in FLASH radiotherapy,” Jun. 18, 2020, https://intraop.com/news-events/lausanne-university-flash-radiotherapy-collaboration/. [cited by applicant]
M.-C. Vozenin et al., “Biological Benefits of Ultra-high Dose Rate FLASH Radiotherapy: Sleeping Beauty Awoken,” Clin Oncol (R Coll Radiol). Author manuscript; available in PMC Nov. 12, 2019. https://www.ncbi.nlm.nih.gov… [cited by applicant]
Efstathios Kamperis et al., “A FLASH back to radiotherapy's past and then fast forward to the future,” J Cancer Prev Curr Res. 2019; 10(6): 142-144. published Nov. 13, 2019, DOI: 10.15406/jcpcr.2019.10.00407. [cited by applicant]
P. Symonds et al., “FLASH Radiotherapy: The Next Technological Advance in Radiation Therapy?”, Clinical Oncology, vol. 31, Issue 7, p. 405-406, Jul. 1, 2019, The Royal College of Radiologists, Published by Elsevier Ltd.… [cited by applicant]
Swati Girdhani et al., “Abstract LB-280: FLASH: A novel paradigm changing tumor irradiation platform that enhances therapeutic ratio by reducing normal tissue toxicity and activating immune pathways,” Proceedings: AACR … [cited by applicant]
Bazalova-Carter et al., “On the capabilities of conventional x-ray tubes to deliver ultra-high (FLASH) dose rates,” Med. Phys. Dec. 2019; 46 (12):5690-5695, published Oct. 23, 2019, American Association of Physicists in… [cited by applicant]
Manuela Buonanno et al., “Biological effects in normal cells exposed to FLASH dose rate protons,” Radiother Oncol. Author manuscript; available in PMC Oct. 1, 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728238/ … [cited by applicant]
N. Rama et al., “Improved Tumor Control Through T-cell Infiltration Modulated by Ultra-High Dose Rate Proton FLASH Using a Clinical Pencil Beam Scanning Proton System,” International Journal of Radiation Oncology, Biolo… [cited by applicant]
Inserm Press Office, “Radiotherapy ‘flashes’ to reduce side effects,” Press Release, Jul. 16, 2014, https://presse.inserm.fr/en/radiotherapy-flashes-to-reduce-side-effects/13394/. [cited by applicant]
Eric S. Diffenderfer et al., “Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System,” International Journal of Radiation Oncology, Biology, Physics, vol. 106, Issue 2, Feb. 1, 2… [cited by applicant]
Valerie Devillaine, “Radiotherapy and Radiation Biology,” Institut Curie, Apr. 21, 2017, https://institut-curie.org/page/radiotherapy-and-radiation-biology. [cited by applicant]
Imaging Technology News, “ProNova and medPhoton to Offer Next Generation Beam Delivery, Advanced Imaging for Proton Therapy,” Oct. 6, 2014, Wainscot Media, Link: https://www.itnonline.com/content/pronova-and-medphoton-o… [cited by applicant]
Oncolink Team, “Radiation Therapy: Which type is right for me?”, OncoLink Penn Medicine, last reviewed Mar. 3, 2020, Trustees of the University of Pennsylvania, https://www.oncolink.org/cancer-treatment/radiation/introd… [cited by applicant]
Marco Durante et al., “Faster and safer? FLASH ultra-high dose rate in radiotherapy,” Br J Radiol 2018; 91(1082):20170628, British Institute of Radiology, Published Online: Dec. 15, 2017, https://doi.org/10.1259/bjr.201… [cited by applicant]
John R. Fischer, “PMB launches FLASH radiotherapy system for use in clinical trials,” HealthCare Business News, Jun. 29, 2020, DOTmed.com, Inc., https://www.dotmed.com/news/story/51662. [cited by applicant]
Marie-Catherine Vozenin et al., “The advantage of FLASH radiotherapy confirmed in mini-pig and cat-cancer patients,” Clinical Cancer Research, Author Manuscript Published OnlineFirst Jun. 6, 2018, https://clincancerres.… [cited by applicant]