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Title: TU-H-CAMPUS-TeP2-02: FLASH Irradiation Improves the Therapeutic Index Following GI Tract Irradiation

Abstract

Purpose: To investigate and characterize the radiobiological effectiveness of very high dose rate radiotherapy (FLASH) compared to conventional irradiation in an in vivo model. Methods: The gastrointestinal (GI) tract of C57BL/6 mice were irradiated with doses ranging between 10 and 18 Gy using a custom stereotactic jig. A Varian Clinac 21EX was modified to allow dose rates ranging from 0.05 to 240 Gy/s at the position of the mirror. With the gantry at 180 degrees, the jig holding the individual animals was placed above the mirror to take advantage of the reduced source to target distance. Mice were irradiated with 20MeV electrons. Following irradiation, the mice were monitored twice daily for morbidity and daily for weight changes. Results: Mice irradiated with FLASH irradiation had lower weight loss compared to the mice receiving conventional irradiation. Following FLASH irradiation, a maximum weight loss of ∼20% was observed at day 6 with subsequent recovery, while following conventional irradiation, higher weight losses was observed with fewer instances of recovery. Concerning survival, all mice in the conventionally irradiated groups had a 100% mortality in the range of 15.5–18 Gy, while the mice irradiated with FLASH irradiation had a 100% survival in the same range. Conclusion:more » These results have demonstrated proof of principle that FLASH irradiations have a dramatic impact on the overall survival of mice following GI tract irradiations. If the increase in the therapeutic window can be validated and understood, this would revolutionize the field of radiation oncology and lead to increased cure rates with reduced side effects following treatment, resulting in increased quality of life for cancer survivors. Funding: DoD, Award#:W81XWH-14-1-0014, Weston Havens Foundation, Bio-X (Stanford University), the Office of the Dean of the Medical School, the Office of the Provost (Stanford University), and the Swedish Childhood Cancer Foundation; BL and PM are founders of TibaRay,Inc.; BL and PM have received research grants from Varian and RaySearch Laboratory.« less

Authors:
; ; ; ; ; ;  [1]
  1. Stanford University School of Medicine, Palo Alto, California (United States)
Publication Date:
OSTI Identifier:
22654066
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; DISEASE INCIDENCE; DOSE RATES; EDUCATIONAL FACILITIES; IRRADIATION; MICE; RADIOTHERAPY; RATS; SIDE EFFECTS

Citation Formats

Schueler, E, Trovati, S, King, G, Lartey, F, Rafat, M, Loo, B, and Maxim, P. TU-H-CAMPUS-TeP2-02: FLASH Irradiation Improves the Therapeutic Index Following GI Tract Irradiation. United States: N. p., 2016. Web. doi:10.1118/1.4957690.
Schueler, E, Trovati, S, King, G, Lartey, F, Rafat, M, Loo, B, & Maxim, P. TU-H-CAMPUS-TeP2-02: FLASH Irradiation Improves the Therapeutic Index Following GI Tract Irradiation. United States. doi:10.1118/1.4957690.
Schueler, E, Trovati, S, King, G, Lartey, F, Rafat, M, Loo, B, and Maxim, P. Wed . "TU-H-CAMPUS-TeP2-02: FLASH Irradiation Improves the Therapeutic Index Following GI Tract Irradiation". United States. doi:10.1118/1.4957690.
@article{osti_22654066,
title = {TU-H-CAMPUS-TeP2-02: FLASH Irradiation Improves the Therapeutic Index Following GI Tract Irradiation},
author = {Schueler, E and Trovati, S and King, G and Lartey, F and Rafat, M and Loo, B and Maxim, P},
abstractNote = {Purpose: To investigate and characterize the radiobiological effectiveness of very high dose rate radiotherapy (FLASH) compared to conventional irradiation in an in vivo model. Methods: The gastrointestinal (GI) tract of C57BL/6 mice were irradiated with doses ranging between 10 and 18 Gy using a custom stereotactic jig. A Varian Clinac 21EX was modified to allow dose rates ranging from 0.05 to 240 Gy/s at the position of the mirror. With the gantry at 180 degrees, the jig holding the individual animals was placed above the mirror to take advantage of the reduced source to target distance. Mice were irradiated with 20MeV electrons. Following irradiation, the mice were monitored twice daily for morbidity and daily for weight changes. Results: Mice irradiated with FLASH irradiation had lower weight loss compared to the mice receiving conventional irradiation. Following FLASH irradiation, a maximum weight loss of ∼20% was observed at day 6 with subsequent recovery, while following conventional irradiation, higher weight losses was observed with fewer instances of recovery. Concerning survival, all mice in the conventionally irradiated groups had a 100% mortality in the range of 15.5–18 Gy, while the mice irradiated with FLASH irradiation had a 100% survival in the same range. Conclusion: These results have demonstrated proof of principle that FLASH irradiations have a dramatic impact on the overall survival of mice following GI tract irradiations. If the increase in the therapeutic window can be validated and understood, this would revolutionize the field of radiation oncology and lead to increased cure rates with reduced side effects following treatment, resulting in increased quality of life for cancer survivors. Funding: DoD, Award#:W81XWH-14-1-0014, Weston Havens Foundation, Bio-X (Stanford University), the Office of the Dean of the Medical School, the Office of the Provost (Stanford University), and the Swedish Childhood Cancer Foundation; BL and PM are founders of TibaRay,Inc.; BL and PM have received research grants from Varian and RaySearch Laboratory.},
doi = {10.1118/1.4957690},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}