{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:44:51Z","timestamp":1790293491483,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X006611\/1"],"award-info":[{"award-number":["MR\/X006611\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X006611\/1"],"award-info":[{"award-number":["MR\/X006611\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spatially fractionated radiation therapy (SFRT) has therapeutic potential as a priming therapy which boosts tumor control. However, the optimal delivery and spatial fractionation parameters have not been deciphered and the mechanisms at play are not yet fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This paper highlights our preclinical setups for mini\u2010grid SFRT with 6 MeV electrons delivered at conventional to ultrahigh dose rates, using a flexible collimator system. These setups let us explore relevant spatial fractionation parameters to observe their effect on tumor growth and normal tissue toxicity. Preclinical studies here may reveal the parameters of highest clinical relevance for SFRT and combination therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      For preclinical experiments with electron spatial fractionation, 6.5\u00a0mm thick brass collimators were made with 7\u2010 (or 19\u2010) hole hexagonally packed \u2205 0.65\u20102\u00a0mm apertures, with 1.6\u20105\u00a0mm CTC distances. Irradiated EBT\u2010XD Gafchromic film downstream of collimators were analyzed to obtain peak\u2010to\u2010valley dose ratios (PVDR), full width at half maxima (FWHM), and peak doses at various depths in solid water, and at surface when increasing the separations from collimators in air. Male and female C57BL\/6 mice were injected subcutaneously with UPPL1541 bladder cancer cells in the right flank. After 10\u201313 days, a single dose treatment was delivered to the tumors with either \u220514\u00a0mm circular homogeneous field (10\u00a0Gy delivered at 3 kGy s\n                      <jats:sup>\u22121<\/jats:sup>\n                      ), or using a 7\u2010hole (\u2205 of 2 and 5\u00a0mm center\u2010to\u2010center distances) spatially fractionated field; peak doses of 30\u00a0Gy delivered at 820\u00a0Gy s\n                      <jats:sup>\u22121<\/jats:sup>\n                      , 20\u00a0Gy at 860\u00a0Gy s\n                      <jats:sup>\u22121<\/jats:sup>\n                      , and 20\u00a0Gy at\u00a0&lt;\u00a00.1\u00a0Gy s\n                      <jats:sup>\u22121<\/jats:sup>\n                      . Tumor growth and time to triple tumor volume (TTTV) were measured and compared between treatment regimens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Similar PVDRs were obtained with 7\u2010 and 19\u2010hole inserts (35 and\u00a031 at surface, respectively). Peak widths increased with depth, and maximal peak dose rates were\u00a0&gt;\u00a01.8 kGy s\n                      <jats:sup>\u22121<\/jats:sup>\n                      . A displacement in air from the collimator exit decreased PVDRs at the phantom surface; from\u00a032 to\u00a016 at\u00a0\u223c10\u00a0mm distance,\u00a0and to 6 at\u00a0\u223c20\u00a0mm distance. Peak doses also reduced to \u223c57 % at 10\u00a0mm distance, and to\u00a0\u223c33% at 20\u00a0mm distance. Film measurements at the mouse phantom surface produced peak and valley dose rates of\u00a0&gt;\u00a0850\u00a0Gy s\n                      <jats:sup>\u22121<\/jats:sup>\n                      and \u223c60\u00a0Gy s\n                      <jats:sup>\u22121<\/jats:sup>\n                      respectively, with a PVDR\u00a0&gt;\u00a014. Tumor growth delays for spatially fractionated FLASH 30\u00a0Gy (peak dose, with a 2.1\u00a0Gy valley dose, and a 10\u00a0Gy average dose) and homogeneous FLASH 10\u00a0Gy electron irradiation regimens were similar. Both regimens also demonstrated significantly longer TTTV compared to control and spatially fractionated conventional 20\u00a0Gy (peak dose, with a 1.4\u00a0Gy valley dose, and a 6.7\u00a0Gy average dose) regimens (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). No significant differences in body weight and skin damage were observed, indicating acceptable treatment tolerability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Spatially fractionated electron FLASH treatments with 30\u00a0Gy peak doses and 2.1\u00a0Gy valley doses provide effective tumor growth delay and prolonged tumor control akin to 10\u00a0Gy homogeneous irradiations. Here we demonstrate that combining spatial modulation, higher peak doses, and FLASH dose rates can produce favorable tumor response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.70448","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:10:58Z","timestamp":1777018258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A preclinical setup for spatially fractionated radiation therapy with electrons"],"prefix":"10.1002","volume":"53","author":[{"given":"Edward R J F","family":"Taylor","sequence":"first","affiliation":[{"name":"Department of Oncology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Ling","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Oxford  Oxford 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