Trade-off in healthy tissue sparing of FLASH and fractionation in stereotactic proton therapy of lung lesions with transmission beams

Steven Habraken; Sebastiaan Breedveld; Jort Groen; Joost Nuyttens; Mischa Hoogeman

doi:10.1016/j.radonc.2022.08.015

Trade-off in healthy tissue sparing of FLASH and fractionation in stereotactic proton therapy of lung lesions with transmission beams

Steven Habraken^*, Sebastiaan Breedveld, Jort Groen, Joost Nuyttens, Mischa Hoogeman

^*Corresponding author for this work

Radiotherapy

Research output: Contribution to journal › Article › Academic › peer-review

10 Citations (Scopus)

Abstract

Purpose and objective: Besides a dose-rate threshold of 40–100 Gy/s, the FLASH effect may require a dose > 3.5–7 Gy. Even in hypofractioned treatments, with all beams delivered in each fraction (ABEF), most healthy tissue is irradiated to a lower fraction dose. This can be circumvented by single-beam-per-fraction (SBPF) delivery, with a loss of healthy tissue sparing by fractionation. We investigated the trade-off between FLASH and loss of fractionation in SBPF stereotactic proton therapy of lung cancer and determined break-even FLASH-enhancement ratios (FERs). Materials and Methods: Treatment plans for 12 patients were generated. GTV delineations were available and a 5 mm GTV-PTV margin was applied. Equiangular arrangements of 3, 5, 7, and 9 244 MeV proton transmission beams were used. To facilitate SBPF, the number of fractions was equal to the number of beams. Iso-effective fractionation schedules with a single field uniform dose prescription were used: D_95%,PTV = 100%D_pres per beam. All plans were evaluated in terms of dose to lung and conformity of dose to target of FLASH-enhanced biologically equivalent dose (EQD2). Results: Compared to ABEF, SBPF resulted in a median increase of EQD2_mean to healthy lung of 56%, 58%, 55% and 54% in plans with 3, 5, 7 and 9 fractions respectively and of 236%, 78%, 50% and 41% in V_{100% EQD2}, quantifying conformity. This can be compensated for by FERs of at least 1.28, 1.32, 1.30 and 1.23 respectively for EQD2_mean and 1.29, 1.18, 1.28 and 1.15 for V_100%,EQD2. Conclusion: A FLASH effect outweighing the loss of fractionation in SBPF may be achieved in stereotactic lung treatments. The trade-off with fractionation depends on the conditions under which the FLASH effect occurs. Better understanding of the underlying biology and the impact of delivery conditions is needed.

Original language	English
Pages (from-to)	231-237
Number of pages	7
Journal	Radiotherapy and Oncology
Volume	175
DOIs	https://doi.org/10.1016/j.radonc.2022.08.015
Publication status	Published - Oct 2022

Bibliographical note

Funding Information:
The department of radiotherapy of the Erasmus MC Cancer Institute received a research grant from the Dutch cancer society and has research collaborations with Elekta AB, Stockholm, Sweden and Accuray Inc., Sunnyvale, USA. HollandPTC has a research collaboration with Varian, Palo Alto, USA.

Publisher Copyright:
© 2022 The Authors

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10.1016/j.radonc.2022.08.015

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@article{2d3e48204a87445382fcc51f9d1a972d,

title = "Trade-off in healthy tissue sparing of FLASH and fractionation in stereotactic proton therapy of lung lesions with transmission beams",

abstract = "Purpose and objective: Besides a dose-rate threshold of 40–100 Gy/s, the FLASH effect may require a dose > 3.5–7 Gy. Even in hypofractioned treatments, with all beams delivered in each fraction (ABEF), most healthy tissue is irradiated to a lower fraction dose. This can be circumvented by single-beam-per-fraction (SBPF) delivery, with a loss of healthy tissue sparing by fractionation. We investigated the trade-off between FLASH and loss of fractionation in SBPF stereotactic proton therapy of lung cancer and determined break-even FLASH-enhancement ratios (FERs). Materials and Methods: Treatment plans for 12 patients were generated. GTV delineations were available and a 5 mm GTV-PTV margin was applied. Equiangular arrangements of 3, 5, 7, and 9 244 MeV proton transmission beams were used. To facilitate SBPF, the number of fractions was equal to the number of beams. Iso-effective fractionation schedules with a single field uniform dose prescription were used: D95%,PTV = 100%Dpres per beam. All plans were evaluated in terms of dose to lung and conformity of dose to target of FLASH-enhanced biologically equivalent dose (EQD2). Results: Compared to ABEF, SBPF resulted in a median increase of EQD2mean to healthy lung of 56%, 58%, 55% and 54% in plans with 3, 5, 7 and 9 fractions respectively and of 236%, 78%, 50% and 41% in V100% EQD2, quantifying conformity. This can be compensated for by FERs of at least 1.28, 1.32, 1.30 and 1.23 respectively for EQD2mean and 1.29, 1.18, 1.28 and 1.15 for V100%,EQD2. Conclusion: A FLASH effect outweighing the loss of fractionation in SBPF may be achieved in stereotactic lung treatments. The trade-off with fractionation depends on the conditions under which the FLASH effect occurs. Better understanding of the underlying biology and the impact of delivery conditions is needed.",

author = "Steven Habraken and Sebastiaan Breedveld and Jort Groen and Joost Nuyttens and Mischa Hoogeman",

note = "Funding Information: The department of radiotherapy of the Erasmus MC Cancer Institute received a research grant from the Dutch cancer society and has research collaborations with Elekta AB, Stockholm, Sweden and Accuray Inc., Sunnyvale, USA. HollandPTC has a research collaboration with Varian, Palo Alto, USA. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = oct,

doi = "10.1016/j.radonc.2022.08.015",

language = "English",

volume = "175",

pages = "231--237",

journal = "Radiotherapy and Oncology",

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T1 - Trade-off in healthy tissue sparing of FLASH and fractionation in stereotactic proton therapy of lung lesions with transmission beams

AU - Habraken, Steven

AU - Breedveld, Sebastiaan

AU - Groen, Jort

AU - Nuyttens, Joost

AU - Hoogeman, Mischa

N1 - Funding Information: The department of radiotherapy of the Erasmus MC Cancer Institute received a research grant from the Dutch cancer society and has research collaborations with Elekta AB, Stockholm, Sweden and Accuray Inc., Sunnyvale, USA. HollandPTC has a research collaboration with Varian, Palo Alto, USA. Publisher Copyright: © 2022 The Authors

PY - 2022/10

Y1 - 2022/10

N2 - Purpose and objective: Besides a dose-rate threshold of 40–100 Gy/s, the FLASH effect may require a dose > 3.5–7 Gy. Even in hypofractioned treatments, with all beams delivered in each fraction (ABEF), most healthy tissue is irradiated to a lower fraction dose. This can be circumvented by single-beam-per-fraction (SBPF) delivery, with a loss of healthy tissue sparing by fractionation. We investigated the trade-off between FLASH and loss of fractionation in SBPF stereotactic proton therapy of lung cancer and determined break-even FLASH-enhancement ratios (FERs). Materials and Methods: Treatment plans for 12 patients were generated. GTV delineations were available and a 5 mm GTV-PTV margin was applied. Equiangular arrangements of 3, 5, 7, and 9 244 MeV proton transmission beams were used. To facilitate SBPF, the number of fractions was equal to the number of beams. Iso-effective fractionation schedules with a single field uniform dose prescription were used: D95%,PTV = 100%Dpres per beam. All plans were evaluated in terms of dose to lung and conformity of dose to target of FLASH-enhanced biologically equivalent dose (EQD2). Results: Compared to ABEF, SBPF resulted in a median increase of EQD2mean to healthy lung of 56%, 58%, 55% and 54% in plans with 3, 5, 7 and 9 fractions respectively and of 236%, 78%, 50% and 41% in V100% EQD2, quantifying conformity. This can be compensated for by FERs of at least 1.28, 1.32, 1.30 and 1.23 respectively for EQD2mean and 1.29, 1.18, 1.28 and 1.15 for V100%,EQD2. Conclusion: A FLASH effect outweighing the loss of fractionation in SBPF may be achieved in stereotactic lung treatments. The trade-off with fractionation depends on the conditions under which the FLASH effect occurs. Better understanding of the underlying biology and the impact of delivery conditions is needed.

AB - Purpose and objective: Besides a dose-rate threshold of 40–100 Gy/s, the FLASH effect may require a dose > 3.5–7 Gy. Even in hypofractioned treatments, with all beams delivered in each fraction (ABEF), most healthy tissue is irradiated to a lower fraction dose. This can be circumvented by single-beam-per-fraction (SBPF) delivery, with a loss of healthy tissue sparing by fractionation. We investigated the trade-off between FLASH and loss of fractionation in SBPF stereotactic proton therapy of lung cancer and determined break-even FLASH-enhancement ratios (FERs). Materials and Methods: Treatment plans for 12 patients were generated. GTV delineations were available and a 5 mm GTV-PTV margin was applied. Equiangular arrangements of 3, 5, 7, and 9 244 MeV proton transmission beams were used. To facilitate SBPF, the number of fractions was equal to the number of beams. Iso-effective fractionation schedules with a single field uniform dose prescription were used: D95%,PTV = 100%Dpres per beam. All plans were evaluated in terms of dose to lung and conformity of dose to target of FLASH-enhanced biologically equivalent dose (EQD2). Results: Compared to ABEF, SBPF resulted in a median increase of EQD2mean to healthy lung of 56%, 58%, 55% and 54% in plans with 3, 5, 7 and 9 fractions respectively and of 236%, 78%, 50% and 41% in V100% EQD2, quantifying conformity. This can be compensated for by FERs of at least 1.28, 1.32, 1.30 and 1.23 respectively for EQD2mean and 1.29, 1.18, 1.28 and 1.15 for V100%,EQD2. Conclusion: A FLASH effect outweighing the loss of fractionation in SBPF may be achieved in stereotactic lung treatments. The trade-off with fractionation depends on the conditions under which the FLASH effect occurs. Better understanding of the underlying biology and the impact of delivery conditions is needed.

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SN - 0167-8140

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JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

ER -

Trade-off in healthy tissue sparing of FLASH and fractionation in stereotactic proton therapy of lung lesions with transmission beams

Abstract

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