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Optimizing allocation of limited proton fractions via NTCP-optimized combined proton-photon radiotherapy.

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Τίτλος: Optimizing allocation of limited proton fractions via NTCP-optimized combined proton-photon radiotherapy.
Συγγραφείς: Wang W; School of Electrical and Information Engineering, Changsha University of Science and Technology, Changsha, China.; State Key Laboratory of Advanced Electromagnetic Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Wuhan, China.; Department of Radiation Oncology, Medical Center, University of Kansas, Kansas City, USA., Li W; Department of Radiation Oncology, Medical Center, University of Kansas, Kansas City, USA., Lin Y; Department of Radiation Oncology, Medical Center, University of Kansas, Kansas City, USA., Liu X; State Key Laboratory of Advanced Electromagnetic Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Wuhan, China., Qin B; State Key Laboratory of Advanced Electromagnetic Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Wuhan, China. bin.qin@hust.edu.cn., Gao H; Department of Radiation Oncology, Medical Center, University of Kansas, Kansas City, USA. hgao2@kumc.edu.
Πηγή: Physical and engineering sciences in medicine [Phys Eng Sci Med] 2026 Sep; Vol. 49 (3), pp. 1483-1493. Date of Electronic Publication: 2026 Aug 04.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer Country of Publication: Switzerland NLM ID: 101760671 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2662-4737 (Electronic) Linking ISSN: 26624729 NLM ISO Abbreviation: Phys Eng Sci Med Subsets: MEDLINE
Imprint Name(s): Original Publication: Switzerland : Springer, [2020]-
Ιατρικοί όροι (MeSH): Proton Therapy*/methods , Photons*/therapeutic use , Radiotherapy, Intensity-Modulated* , Dose Fractionation, Radiation*, Radiotherapy Planning, Computer-Assisted/methods ; Humans ; Protons ; Radiotherapy Dosage
Περίληψη: Compared to photon radiotherapy (RT), proton RT is less widely available and more costly. To maximize the normal-tissue complication probability (NTCP) benefit of limited proton resources at a population level, this work introduces a novel NTCP-optimized combined proton-photon treatment (NTCP-CPPT) approach that can achieve the OAR-sparing benefits in terms of reaching desired NTCP thresholds with the minimal proton fraction. NTCP-optimized intensity-modulated proton therapy (NTCP-IMPT) and NTCP-optimized intensity-modulated radiation therapy (NTCP-IMRT) plans are generated via the NTCP-optimized treatment planning based on physical dose and NTCP objectives. For each patient, a minimal proton fraction is determined for the NTCP-CPPT plan as a combination of NTCP-IMPT and NTCP-IMRT plans, while still retaining the sum-NTCP threshold for the patient to be justified for the proton access. For comparison, conventional CPPT (CONV-CPPT) plans are obtained by a combination of conventional IMRT (CONV-IMRT) and conventional IMPT (CONV-IMPT) plans that are solely optimized based on physical dose optimization. Compared to CONV-CPPT, NTCP-CPPT reduced the average proton fractions from 18 to 3 without compromising physical dose objectives, while both NTCP-CPPT and CONV-CPPT plans maintained a sum-NTCP below 20% relative to CONV-IMRT. Additionally, NTCP-CPPT, using an average of 22 proton fractions out of 35, maintained the same sum-NTCP as CONV-IMPT required 35 proton fractions. To increase patient access to proton RT, a novel combined proton-photon treatment called NTCP-CPPT is proposed that can provide a minimal number of proton fractions while still retaining sufficient OAR-sparing benefits to justify the proton access.
(© 2026. The Author(s).)
Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethics approval: This retrospective study was approved by the Institutional Review Board of UT Southwestern Medical Center. The requirement for informed consent was waived because the study involved retrospective analysis of existing de-identified clinical imaging data.
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Radiother Oncol. 2013 Jun;107(3):267-73. (PMID: 23759662)
Int J Radiat Oncol Biol Phys. 2020 Nov 1;108(3):792-801. (PMID: 32361008)
Lancet Oncol. 2023 Jun;24(6):e245-e254. (PMID: 37269856)
Radiother Oncol. 2010 Apr;95(1):45-53. (PMID: 20106540)
Radiother Oncol. 2016 Dec;121(3):381-386. (PMID: 27641784)
Radiother Oncol. 2024 Oct;199:110441. (PMID: 39069084)
Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):589-96. (PMID: 18793962)
Phys Med Biol. 2024 May 20;69(11):. (PMID: 38688290)
Nature. 2017 Sep 25;549(7673):451-453. (PMID: 28959981)
Int J Radiat Oncol Biol Phys. 2017 Dec 1;99(5):1078-1082. (PMID: 28939229)
Radiother Oncol. 2020 Apr;145:81-87. (PMID: 31923713)
Phys Med Biol. 2019 May 08;64(10):105003. (PMID: 30978714)
Radiother Oncol. 2022 Sep;174:23-29. (PMID: 35788354)
Med Phys. 2022 Aug;49(8):5374-5386. (PMID: 35561077)
Med Phys. 2023 Jun;50(6):3311-3323. (PMID: 36786202)
Adv Drug Deliv Rev. 2017 Jan 15;109:1-2. (PMID: 28189183)
Radiother Oncol. 2020 Oct;151:206-213. (PMID: 32768508)
Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):392-8. (PMID: 11567813)
Radiother Oncol. 2017 Aug;124(2):263-270. (PMID: 28411963)
Clin Oncol (R Coll Radiol). 2018 May;30(5):299-306. (PMID: 29452724)
Med Phys. 2025 Mar;52(3):1399-1407. (PMID: 39625225)
Adv Drug Deliv Rev. 2017 Jan 15;109:26-44. (PMID: 27919760)
Cancer Radiother. 2005 May;9(3):161-74. (PMID: 15979920)
Int J Radiat Oncol Biol Phys. 2017 Apr 1;97(5):1087-1094. (PMID: 28332994)
Radiother Oncol. 2018 Jul;128(1):133-138. (PMID: 29370987)
Med Phys. 2017 Jun;44(6):2556-2568. (PMID: 28370020)
Med Phys. 2012 Aug;39(8):5248-56. (PMID: 22894449)
Phys Med Biol. 2018 Nov 12;63(22):22TR02. (PMID: 30418942)
JAMA Oncol. 2020 Feb 1;6(2):237-246. (PMID: 31876914)
Med Phys. 2023 Aug;50(8):5189-5200. (PMID: 37099491)
Phys Med Biol. 2019 Mar 12;64(6):065011. (PMID: 30641502)
Med Phys. 2023 Jun;50(6):3258-3273. (PMID: 36965109)
Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):224-233. (PMID: 26611874)
Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):944-54. (PMID: 17889276)
Radiother Oncol. 2020 Nov;152:151-162. (PMID: 31431365)
Int J Radiat Oncol Biol Phys. 1995 Feb 1;31(3):467-76. (PMID: 7852108)
Int J Radiat Oncol Biol Phys. 2021 Sep 1;111(1):196-207. (PMID: 33848609)
Grant Information: R01 CA261964 United States CA NCI NIH HHS; R37 CA250921 United States CA NCI NIH HHS; R37CA250921 Foundation for the National Institutes of Health; R01CA261964 Foundation for the National Institutes of Health
Contributed Indexing: Keywords: Combined proton–photon radiotherapy; Minimize proton fractions; NTCP optimization
Substance Nomenclature: 0 (Protons)
Entry Date(s): Date Created: 20260804 Date Completed: 20261005 Latest Revision: 20261008
Update Code: 20261008
PubMed Central ID: PMC13638690
DOI: 10.1007/s13246-026-01759-7
PMID: 42550398
Βάση Δεδομένων: MEDLINE
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  Data: Optimizing allocation of limited proton fractions via NTCP-optimized combined proton-photon radiotherapy.
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  Data: <searchLink fieldCode="AU" term="%22Wang+W%22">Wang W</searchLink>; School of Electrical and Information Engineering, Changsha University of Science and Technology, Changsha, China.; State Key Laboratory of Advanced Electromagnetic Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Wuhan, China.; Department of Radiation Oncology, Medical Center, University of Kansas, Kansas City, USA.<br /><searchLink fieldCode="AU" term="%22Li+W%22">Li W</searchLink>; Department of Radiation Oncology, Medical Center, University of Kansas, Kansas City, USA.<br /><searchLink fieldCode="AU" term="%22Lin+Y%22">Lin Y</searchLink>; Department of Radiation Oncology, Medical Center, University of Kansas, Kansas City, USA.<br /><searchLink fieldCode="AU" term="%22Liu+X%22">Liu X</searchLink>; State Key Laboratory of Advanced Electromagnetic Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Wuhan, China.<br /><searchLink fieldCode="AU" term="%22Qin+B%22">Qin B</searchLink>; State Key Laboratory of Advanced Electromagnetic Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Wuhan, China. bin.qin@hust.edu.cn.<br /><searchLink fieldCode="AU" term="%22Gao+H%22">Gao H</searchLink>; Department of Radiation Oncology, Medical Center, University of Kansas, Kansas City, USA. hgao2@kumc.edu.
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  Data: <searchLink fieldCode="MM" term="%22Proton+Therapy%22">Proton Therapy*</searchLink>/<searchLink fieldCode="MM" term="%22Proton+Therapy+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22Photons%22">Photons*</searchLink>/<searchLink fieldCode="MM" term="%22Photons+therapeutic+use%22">therapeutic use</searchLink> <br /><searchLink fieldCode="MM" term="%22Radiotherapy%2C+Intensity-Modulated%22">Radiotherapy, Intensity-Modulated*</searchLink> <br /><searchLink fieldCode="MM" term="%22Dose+Fractionation%2C+Radiation%22">Dose Fractionation, Radiation*</searchLink><br /><searchLink fieldCode="MH" term="%22Radiotherapy+Planning%2C+Computer-Assisted%22">Radiotherapy Planning, Computer-Assisted</searchLink>/<searchLink fieldCode="MH" term="%22Radiotherapy+Planning%2C+Computer-Assisted+methods%22">methods</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Protons%22">Protons</searchLink> ; <searchLink fieldCode="MH" term="%22Radiotherapy+Dosage%22">Radiotherapy Dosage</searchLink>
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  Data: Compared to photon radiotherapy (RT), proton RT is less widely available and more costly. To maximize the normal-tissue complication probability (NTCP) benefit of limited proton resources at a population level, this work introduces a novel NTCP-optimized combined proton-photon treatment (NTCP-CPPT) approach that can achieve the OAR-sparing benefits in terms of reaching desired NTCP thresholds with the minimal proton fraction. NTCP-optimized intensity-modulated proton therapy (NTCP-IMPT) and NTCP-optimized intensity-modulated radiation therapy (NTCP-IMRT) plans are generated via the NTCP-optimized treatment planning based on physical dose and NTCP objectives. For each patient, a minimal proton fraction is determined for the NTCP-CPPT plan as a combination of NTCP-IMPT and NTCP-IMRT plans, while still retaining the sum-NTCP threshold for the patient to be justified for the proton access. For comparison, conventional CPPT (CONV-CPPT) plans are obtained by a combination of conventional IMRT (CONV-IMRT) and conventional IMPT (CONV-IMPT) plans that are solely optimized based on physical dose optimization. Compared to CONV-CPPT, NTCP-CPPT reduced the average proton fractions from 18 to 3 without compromising physical dose objectives, while both NTCP-CPPT and CONV-CPPT plans maintained a sum-NTCP below 20% relative to CONV-IMRT. Additionally, NTCP-CPPT, using an average of 22 proton fractions out of 35, maintained the same sum-NTCP as CONV-IMPT required 35 proton fractions. To increase patient access to proton RT, a novel combined proton-photon treatment called NTCP-CPPT is proposed that can provide a minimal number of proton fractions while still retaining sufficient OAR-sparing benefits to justify the proton access.<br /> (© 2026. The Author(s).)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethics approval: This retrospective study was approved by the Institutional Review Board of UT Southwestern Medical Center. The requirement for informed consent was waived because the study involved retrospective analysis of existing de-identified clinical imaging data.
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  Label: References
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  Data: Radiother Oncol. 2005 May;75(2):179-85. (PMID: <searchLink fieldCode="PM" term="%2215885828%22">15885828)</searchLink><br />Radiother Oncol. 2013 Jun;107(3):267-73. (PMID: <searchLink fieldCode="PM" term="%2223759662%22">23759662)</searchLink><br />Int J Radiat Oncol Biol Phys. 2020 Nov 1;108(3):792-801. (PMID: <searchLink fieldCode="PM" term="%2232361008%22">32361008)</searchLink><br />Lancet Oncol. 2023 Jun;24(6):e245-e254. (PMID: <searchLink fieldCode="PM" term="%2237269856%22">37269856)</searchLink><br />Radiother Oncol. 2010 Apr;95(1):45-53. (PMID: <searchLink fieldCode="PM" term="%2220106540%22">20106540)</searchLink><br />Radiother Oncol. 2016 Dec;121(3):381-386. (PMID: <searchLink fieldCode="PM" term="%2227641784%22">27641784)</searchLink><br />Radiother Oncol. 2024 Oct;199:110441. (PMID: <searchLink fieldCode="PM" term="%2239069084%22">39069084)</searchLink><br />Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):589-96. (PMID: <searchLink fieldCode="PM" term="%2218793962%22">18793962)</searchLink><br />Phys Med Biol. 2024 May 20;69(11):. (PMID: <searchLink fieldCode="PM" term="%2238688290%22">38688290)</searchLink><br />Nature. 2017 Sep 25;549(7673):451-453. (PMID: <searchLink fieldCode="PM" term="%2228959981%22">28959981)</searchLink><br />Int J Radiat Oncol Biol Phys. 2017 Dec 1;99(5):1078-1082. (PMID: <searchLink fieldCode="PM" term="%2228939229%22">28939229)</searchLink><br />Radiother Oncol. 2020 Apr;145:81-87. (PMID: <searchLink fieldCode="PM" term="%2231923713%22">31923713)</searchLink><br />Phys Med Biol. 2019 May 08;64(10):105003. (PMID: <searchLink fieldCode="PM" term="%2230978714%22">30978714)</searchLink><br />Radiother Oncol. 2022 Sep;174:23-29. (PMID: <searchLink fieldCode="PM" term="%2235788354%22">35788354)</searchLink><br />Med Phys. 2022 Aug;49(8):5374-5386. (PMID: <searchLink fieldCode="PM" term="%2235561077%22">35561077)</searchLink><br />Med Phys. 2023 Jun;50(6):3311-3323. (PMID: <searchLink fieldCode="PM" term="%2236786202%22">36786202)</searchLink><br />Adv Drug Deliv Rev. 2017 Jan 15;109:1-2. (PMID: <searchLink fieldCode="PM" term="%2228189183%22">28189183)</searchLink><br />Radiother Oncol. 2020 Oct;151:206-213. (PMID: <searchLink fieldCode="PM" term="%2232768508%22">32768508)</searchLink><br />Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):392-8. (PMID: <searchLink fieldCode="PM" term="%2211567813%22">11567813)</searchLink><br />Radiother Oncol. 2017 Aug;124(2):263-270. (PMID: <searchLink fieldCode="PM" term="%2228411963%22">28411963)</searchLink><br />Clin Oncol (R Coll Radiol). 2018 May;30(5):299-306. (PMID: <searchLink fieldCode="PM" term="%2229452724%22">29452724)</searchLink><br />Med Phys. 2025 Mar;52(3):1399-1407. (PMID: <searchLink fieldCode="PM" term="%2239625225%22">39625225)</searchLink><br />Adv Drug Deliv Rev. 2017 Jan 15;109:26-44. (PMID: <searchLink fieldCode="PM" term="%2227919760%22">27919760)</searchLink><br />Cancer Radiother. 2005 May;9(3):161-74. (PMID: <searchLink fieldCode="PM" term="%2215979920%22">15979920)</searchLink><br />Int J Radiat Oncol Biol Phys. 2017 Apr 1;97(5):1087-1094. (PMID: <searchLink fieldCode="PM" term="%2228332994%22">28332994)</searchLink><br />Radiother Oncol. 2018 Jul;128(1):133-138. (PMID: <searchLink fieldCode="PM" term="%2229370987%22">29370987)</searchLink><br />Med Phys. 2017 Jun;44(6):2556-2568. (PMID: <searchLink fieldCode="PM" term="%2228370020%22">28370020)</searchLink><br />Med Phys. 2012 Aug;39(8):5248-56. (PMID: <searchLink fieldCode="PM" term="%2222894449%22">22894449)</searchLink><br />Phys Med Biol. 2018 Nov 12;63(22):22TR02. (PMID: <searchLink fieldCode="PM" term="%2230418942%22">30418942)</searchLink><br />JAMA Oncol. 2020 Feb 1;6(2):237-246. (PMID: <searchLink fieldCode="PM" term="%2231876914%22">31876914)</searchLink><br />Med Phys. 2023 Aug;50(8):5189-5200. (PMID: <searchLink fieldCode="PM" term="%2237099491%22">37099491)</searchLink><br />Phys Med Biol. 2019 Mar 12;64(6):065011. (PMID: <searchLink fieldCode="PM" term="%2230641502%22">30641502)</searchLink><br />Med Phys. 2023 Jun;50(6):3258-3273. (PMID: <searchLink fieldCode="PM" term="%2236965109%22">36965109)</searchLink><br />Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):224-233. (PMID: <searchLink fieldCode="PM" term="%2226611874%22">26611874)</searchLink><br />Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):944-54. (PMID: <searchLink fieldCode="PM" term="%2217889276%22">17889276)</searchLink><br />Radiother Oncol. 2020 Nov;152:151-162. (PMID: <searchLink fieldCode="PM" term="%2231431365%22">31431365)</searchLink><br />Int J Radiat Oncol Biol Phys. 1995 Feb 1;31(3):467-76. (PMID: <searchLink fieldCode="PM" term="%227852108%22">7852108)</searchLink><br />Int J Radiat Oncol Biol Phys. 2021 Sep 1;111(1):196-207. (PMID: <searchLink fieldCode="PM" term="%2233848609%22">33848609)</searchLink>
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