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Comparable Long-Term Tumor Control for Hypofractionated FLASH Versus Conventional Radiation Therapy in an Immunocompetent Rat Glioma Model

Konradsson, Elise LU ; Liljedahl, Emma LU ; Gustafsson, Emma LU ; Adrian, Gabriel LU orcid ; Beyer, Sarah LU ; Ilaahi, Suhayb Ehsaan ; Petersson, Kristoffer LU ; Ceberg, Crister LU orcid and Nittby Redebrandt, Henrietta LU (2022) In Advances in Radiation Oncology 7(6).
Abstract

Purpose: To ensure a clinical translation of FLASH radiation therapy (FLASH-RT) for a specific tumor type, studies on tumor control and toxicity within the same biological system are needed. In this study, our objective was to evaluate tumor control and toxicity for hypofractionated FLASH-RT and conventional radiation therapy (CONV-RT) in an immunocompetent rat glioma model. Methods and Materials: Fisher 344 rats (N = 68) were inoculated subcutaneously with NS1 glioma cells and randomized into groups (n = 9-10 per group). CONV-RT (∼8 Gy/min) or FLASH-RT (70-90 Gy/s) was administered in 3 fractions of either 8 Gy, 12.5 Gy, or 15 Gy using a 10-MeV electron beam. The maximum tumor diameter was measured weekly, and overall survival was... (More)

Purpose: To ensure a clinical translation of FLASH radiation therapy (FLASH-RT) for a specific tumor type, studies on tumor control and toxicity within the same biological system are needed. In this study, our objective was to evaluate tumor control and toxicity for hypofractionated FLASH-RT and conventional radiation therapy (CONV-RT) in an immunocompetent rat glioma model. Methods and Materials: Fisher 344 rats (N = 68) were inoculated subcutaneously with NS1 glioma cells and randomized into groups (n = 9-10 per group). CONV-RT (∼8 Gy/min) or FLASH-RT (70-90 Gy/s) was administered in 3 fractions of either 8 Gy, 12.5 Gy, or 15 Gy using a 10-MeV electron beam. The maximum tumor diameter was measured weekly, and overall survival was determined until day 100. Long-term tumor control was defined as no evident tumor on day 100. Animals were evaluated for acute dermal side effects at 2 to 5 weeks after completed RT and for late dermal side effects at 3 months after initiation of treatment. Results: Survival was significantly increased in all irradiated groups compared with control animals (P <.001). In general, irradiated tumors started to shrink at 1 week post–completed RT. In 40% (23 of 58) of the irradiated animals, long-term tumor control was achieved. Radiation-induced skin toxic effects were mild and consisted of hair loss, erythema, and dry desquamation. No severe toxic effect was observed. There was no significant difference between FLASH-RT and CONV-RT in overall survival, acute side effects, or late side effects for any of the dose levels. Conclusions: This study shows that hypofractionated FLASH-RT results in long-term tumor control rates similar to those of CONV-RT for the treatment of large subcutaneous glioblastomas in immunocompetent rats. Neither treatment technique induced severe skin toxic effects. Consequently, no significant difference in toxicity could be resolved, suggesting that higher doses may be required to detect a FLASH sparing of skin.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Advances in Radiation Oncology
volume
7
issue
6
article number
101011
publisher
Elsevier
external identifiers
  • scopus:85138549618
  • pmid:36092986
ISSN
2452-1094
DOI
10.1016/j.adro.2022.101011
language
English
LU publication?
yes
id
e4f9edf9-0bab-41b2-9990-520183a9c06d
date added to LUP
2022-12-12 11:57:28
date last changed
2024-06-15 00:10:10
@article{e4f9edf9-0bab-41b2-9990-520183a9c06d,
  abstract     = {{<p>Purpose: To ensure a clinical translation of FLASH radiation therapy (FLASH-RT) for a specific tumor type, studies on tumor control and toxicity within the same biological system are needed. In this study, our objective was to evaluate tumor control and toxicity for hypofractionated FLASH-RT and conventional radiation therapy (CONV-RT) in an immunocompetent rat glioma model. Methods and Materials: Fisher 344 rats (N = 68) were inoculated subcutaneously with NS1 glioma cells and randomized into groups (n = 9-10 per group). CONV-RT (∼8 Gy/min) or FLASH-RT (70-90 Gy/s) was administered in 3 fractions of either 8 Gy, 12.5 Gy, or 15 Gy using a 10-MeV electron beam. The maximum tumor diameter was measured weekly, and overall survival was determined until day 100. Long-term tumor control was defined as no evident tumor on day 100. Animals were evaluated for acute dermal side effects at 2 to 5 weeks after completed RT and for late dermal side effects at 3 months after initiation of treatment. Results: Survival was significantly increased in all irradiated groups compared with control animals (P &lt;.001). In general, irradiated tumors started to shrink at 1 week post–completed RT. In 40% (23 of 58) of the irradiated animals, long-term tumor control was achieved. Radiation-induced skin toxic effects were mild and consisted of hair loss, erythema, and dry desquamation. No severe toxic effect was observed. There was no significant difference between FLASH-RT and CONV-RT in overall survival, acute side effects, or late side effects for any of the dose levels. Conclusions: This study shows that hypofractionated FLASH-RT results in long-term tumor control rates similar to those of CONV-RT for the treatment of large subcutaneous glioblastomas in immunocompetent rats. Neither treatment technique induced severe skin toxic effects. Consequently, no significant difference in toxicity could be resolved, suggesting that higher doses may be required to detect a FLASH sparing of skin.</p>}},
  author       = {{Konradsson, Elise and Liljedahl, Emma and Gustafsson, Emma and Adrian, Gabriel and Beyer, Sarah and Ilaahi, Suhayb Ehsaan and Petersson, Kristoffer and Ceberg, Crister and Nittby Redebrandt, Henrietta}},
  issn         = {{2452-1094}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{6}},
  publisher    = {{Elsevier}},
  series       = {{Advances in Radiation Oncology}},
  title        = {{Comparable Long-Term Tumor Control for Hypofractionated FLASH Versus Conventional Radiation Therapy in an Immunocompetent Rat Glioma Model}},
  url          = {{http://dx.doi.org/10.1016/j.adro.2022.101011}},
  doi          = {{10.1016/j.adro.2022.101011}},
  volume       = {{7}},
  year         = {{2022}},
}