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Investigating the therapeutic potential of FLASH radiotherapy – a treatment planning study

Hörberger, Filip LU ; Petersson, Kristoffer LU ; Ceberg, Sofie LU ; Bäck, Sven LU ; Adrian, Gabriel LU orcid and Ceberg, Crister LU orcid (2025) In Radiotherapy and Oncology 209.
Abstract

Purpose/Background: Ultra-high dose rate radiotherapy (RT) has shown potential for differential normal tissue (NT) sparing (a phenomenon termed the “FLASH effect”), particularly for larger fraction doses (>5 Gy). However, transitioning to hypofractionation may increase late-reacting NT toxicity, counteracting the FLASH effect. This study evaluates whether FLASH-RT can provide netsparing for organs at risk (OARs) and NT within the PTV under the assumption of standard-of-care dose-conformity. Material/Methods: Five patients per tumor-site (breast, head-and-neck, prostate, and glioblastoma) were analyzed. Using the Linear-Quadratic model, dose-distributions with higher dose per fraction were derived from standard schedules while... (More)

Purpose/Background: Ultra-high dose rate radiotherapy (RT) has shown potential for differential normal tissue (NT) sparing (a phenomenon termed the “FLASH effect”), particularly for larger fraction doses (>5 Gy). However, transitioning to hypofractionation may increase late-reacting NT toxicity, counteracting the FLASH effect. This study evaluates whether FLASH-RT can provide netsparing for organs at risk (OARs) and NT within the PTV under the assumption of standard-of-care dose-conformity. Material/Methods: Five patients per tumor-site (breast, head-and-neck, prostate, and glioblastoma) were analyzed. Using the Linear-Quadratic model, dose-distributions with higher dose per fraction were derived from standard schedules while maintaining tumor control efficacy. FLASH-modified dose-distributions were simulated voxel-by-voxel using logistic regression-based dose-modifying factors modeled from preclinical data. These plans were converted to standard fractionation equivalents for radiobiological comparisons of NT damage. Netsparing was defined as the difference in OAR dose-volume histogram parameters between standard and FLASH-modified plans, normalized to the prescribed dose. Commonly used α/β-ratios for tumors and late-reacting NT were applied. Results: The netsparing for OARs and PTV varied strongly by tumor location. Breast and prostate cases showed positive netsparing, indicating that the FLASH effect outweighed increased toxicity. Even under a conservative scenario (higher α/βT vs. α/βNT), most OARs showed positive netsparing. In glioblastoma and head-and-neck cases, no netsparing was observed, indicating increased toxicity even with FLASH induced NT-sparing. Conclusion: FLASH-RT appears to be beneficial for tumor sites where α/βT ≲ α/βNT, such as breast and prostate. However, not all tumor sites may benefit from FLASH-RT, highlighting the need for site-specific consideration for FLASH-RT implementation.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
FLASH radiotherapy, Hypofractionation, Late-reacting normal tissue toxicity, Netsparing
in
Radiotherapy and Oncology
volume
209
article number
110947
publisher
Elsevier
external identifiers
  • pmid:40409370
  • scopus:105006650114
ISSN
0167-8140
DOI
10.1016/j.radonc.2025.110947
language
English
LU publication?
yes
id
04ffc18d-e78b-4bf8-affd-75ad797e6a05
date added to LUP
2025-07-17 09:46:28
date last changed
2025-07-18 02:22:10
@article{04ffc18d-e78b-4bf8-affd-75ad797e6a05,
  abstract     = {{<p>Purpose/Background: Ultra-high dose rate radiotherapy (RT) has shown potential for differential normal tissue (NT) sparing (a phenomenon termed the “FLASH effect”), particularly for larger fraction doses (&gt;5 Gy). However, transitioning to hypofractionation may increase late-reacting NT toxicity, counteracting the FLASH effect. This study evaluates whether FLASH-RT can provide netsparing for organs at risk (OARs) and NT within the PTV under the assumption of standard-of-care dose-conformity. Material/Methods: Five patients per tumor-site (breast, head-and-neck, prostate, and glioblastoma) were analyzed. Using the Linear-Quadratic model, dose-distributions with higher dose per fraction were derived from standard schedules while maintaining tumor control efficacy. FLASH-modified dose-distributions were simulated voxel-by-voxel using logistic regression-based dose-modifying factors modeled from preclinical data. These plans were converted to standard fractionation equivalents for radiobiological comparisons of NT damage. Netsparing was defined as the difference in OAR dose-volume histogram parameters between standard and FLASH-modified plans, normalized to the prescribed dose. Commonly used α/β-ratios for tumors and late-reacting NT were applied. Results: The netsparing for OARs and PTV varied strongly by tumor location. Breast and prostate cases showed positive netsparing, indicating that the FLASH effect outweighed increased toxicity. Even under a conservative scenario (higher α/β<sub>T</sub> vs. α/β<sub>NT</sub>), most OARs showed positive netsparing. In glioblastoma and head-and-neck cases, no netsparing was observed, indicating increased toxicity even with FLASH induced NT-sparing. Conclusion: FLASH-RT appears to be beneficial for tumor sites where α/β<sub>T</sub> ≲ α/β<sub>NT</sub>, such as breast and prostate. However, not all tumor sites may benefit from FLASH-RT, highlighting the need for site-specific consideration for FLASH-RT implementation.</p>}},
  author       = {{Hörberger, Filip and Petersson, Kristoffer and Ceberg, Sofie and Bäck, Sven and Adrian, Gabriel and Ceberg, Crister}},
  issn         = {{0167-8140}},
  keywords     = {{FLASH radiotherapy; Hypofractionation; Late-reacting normal tissue toxicity; Netsparing}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Radiotherapy and Oncology}},
  title        = {{Investigating the therapeutic potential of FLASH radiotherapy – a treatment planning study}},
  url          = {{http://dx.doi.org/10.1016/j.radonc.2025.110947}},
  doi          = {{10.1016/j.radonc.2025.110947}},
  volume       = {{209}},
  year         = {{2025}},
}