Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Not All Tumors Are Alike : Varying Efficacy of FLASH Across Tumor Types and Oxygenation Status in Spheroid Models

Dela, Rebecka LU ; Lemos Da Silva, Liliana LU orcid ; Beyer, Sarah LU ; Sørensen, Brita Singers ; Poulsen, Per ; Konradsson, Elise LU ; Hörberger, Filip LU ; Petersson, Kristoffer LU ; Ceberg, Crister LU orcid and Adrian, Gabriel LU orcid (2025) In The British journal of radiology
Abstract

OBJECTIVES: Ultra-high dose rate irradiation (UHDR) has been shown to spare normal tissue in various model systems. This study evaluates its potential to sterilize cancer cells using spheroid tumor models.

METHODS: Spheroids from glioblastoma (U87), hypopharyngeal squamous cell carcinoma (two sizes, FaDusmall and FaDularge) and breast adenocarcinoma (T47D) cells were irradiated with electron beams using UHDR (>200Gy/s) or conventional dose rate (CONV,∼0.1 Gy/s) exposures under ambient or reduced oxygen (1%) conditions. U87 and FaDusmall were also irradiated with protons. Spheroids were monitored using imaging for up to 100 days to determine the dose required to cure 50% of spheroids (SCD50). These data were used to calculate... (More)

OBJECTIVES: Ultra-high dose rate irradiation (UHDR) has been shown to spare normal tissue in various model systems. This study evaluates its potential to sterilize cancer cells using spheroid tumor models.

METHODS: Spheroids from glioblastoma (U87), hypopharyngeal squamous cell carcinoma (two sizes, FaDusmall and FaDularge) and breast adenocarcinoma (T47D) cells were irradiated with electron beams using UHDR (>200Gy/s) or conventional dose rate (CONV,∼0.1 Gy/s) exposures under ambient or reduced oxygen (1%) conditions. U87 and FaDusmall were also irradiated with protons. Spheroids were monitored using imaging for up to 100 days to determine the dose required to cure 50% of spheroids (SCD50). These data were used to calculate dose-modifying factor estimates for UHDR at the 50% survival level (DMFSCD50).

RESULTS: A total of 3,230 spheroids were analyzed. Under ambient oxygen tension, UHDR and CONV showed no significant differences in U87 (DMFSCD50=0.98, p = 0.47), FaDusmall (DMFSCD50=1.01, p = 0.75), and T47D (DMFSCD50=1.04, p = 0.25), regardless of electron or proton irradiation. Under reduced oxygen levels, significantly higher UHDR doses were required to sterilize the spheroids, with DMFSCD50 1.14 (U87, p < 0.01), 1.07 (FaDusmall, p = 0.02) and 1.13 (T47D, p < 0.01) . FaDularge-spheroids irradiated under ambient oxygen showed a DMFSCD50 of 1.66 (p < 0.001).

CONCLUSION: Using spheroid tumor models with long follow-up, we demonstrate that efficacy of UHDR varies across cancer types and conditions. Whereas small spheroids exhibit iso-efficacy, both reduced oxygen tension and increased spheroid size lead to higher DMF.

ADVANCES IN KNOWLEDGE: This preclinical study suggests that tumor iso-efficacy with UHDR may not hold true for all cancer types and is associated with oxygen level.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
The British journal of radiology
publisher
British Institute of Radiology
external identifiers
  • pmid:40878442
ISSN
1748-880X
DOI
10.1093/bjr/tqaf219
language
English
LU publication?
yes
additional info
© The Author(s) 2025. Published by Oxford University Press on behalf of the British Institute of Radiology.
id
0f1a0377-3048-423a-94f6-3054ecd7082a
date added to LUP
2025-11-11 07:28:03
date last changed
2025-11-11 07:28:03
@article{0f1a0377-3048-423a-94f6-3054ecd7082a,
  abstract     = {{<p>OBJECTIVES: Ultra-high dose rate irradiation (UHDR) has been shown to spare normal tissue in various model systems. This study evaluates its potential to sterilize cancer cells using spheroid tumor models.</p><p>METHODS: Spheroids from glioblastoma (U87), hypopharyngeal squamous cell carcinoma (two sizes, FaDusmall and FaDularge) and breast adenocarcinoma (T47D) cells were irradiated with electron beams using UHDR (&gt;200Gy/s) or conventional dose rate (CONV,∼0.1 Gy/s) exposures under ambient or reduced oxygen (1%) conditions. U87 and FaDusmall were also irradiated with protons. Spheroids were monitored using imaging for up to 100 days to determine the dose required to cure 50% of spheroids (SCD50). These data were used to calculate dose-modifying factor estimates for UHDR at the 50% survival level (DMFSCD50).</p><p>RESULTS: A total of 3,230 spheroids were analyzed. Under ambient oxygen tension, UHDR and CONV showed no significant differences in U87 (DMFSCD50=0.98, p = 0.47), FaDusmall (DMFSCD50=1.01, p = 0.75), and T47D (DMFSCD50=1.04, p = 0.25), regardless of electron or proton irradiation. Under reduced oxygen levels, significantly higher UHDR doses were required to sterilize the spheroids, with DMFSCD50 1.14 (U87, p &lt; 0.01), 1.07 (FaDusmall, p = 0.02) and 1.13 (T47D, p &lt; 0.01) . FaDularge-spheroids irradiated under ambient oxygen showed a DMFSCD50 of 1.66 (p &lt; 0.001).</p><p>CONCLUSION: Using spheroid tumor models with long follow-up, we demonstrate that efficacy of UHDR varies across cancer types and conditions. Whereas small spheroids exhibit iso-efficacy, both reduced oxygen tension and increased spheroid size lead to higher DMF.</p><p>ADVANCES IN KNOWLEDGE: This preclinical study suggests that tumor iso-efficacy with UHDR may not hold true for all cancer types and is associated with oxygen level.</p>}},
  author       = {{Dela, Rebecka and Lemos Da Silva, Liliana and Beyer, Sarah and Sørensen, Brita Singers and Poulsen, Per and Konradsson, Elise and Hörberger, Filip and Petersson, Kristoffer and Ceberg, Crister and Adrian, Gabriel}},
  issn         = {{1748-880X}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{British Institute of Radiology}},
  series       = {{The British journal of radiology}},
  title        = {{Not All Tumors Are Alike : Varying Efficacy of FLASH Across Tumor Types and Oxygenation Status in Spheroid Models}},
  url          = {{http://dx.doi.org/10.1093/bjr/tqaf219}},
  doi          = {{10.1093/bjr/tqaf219}},
  year         = {{2025}},
}