Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model

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Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model. / Sørensen, Brita Singers; Sitarz, Mateusz Krzysztof; Ankjærgaard, Christina et al.

I: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 17.05.2022.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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Sørensen BS, Sitarz MK, Ankjærgaard C, Johansen JG, Andersen CE, Kanouta E et al. Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2022 maj 17. https://doi.org/10.1016/j.radonc.2022.05.014

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Sørensen, Brita Singers ; Sitarz, Mateusz Krzysztof ; Ankjærgaard, Christina et al. / Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model. I: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2022.

Bibtex

@article{120195146278410ca6b909ac68448cde,
title = "Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model",
abstract = "PURPOSE: Preclinical studies indicate a normal tissue sparing effect when ultra-high dose rate (FLASH) radiation is used, while tumor response is maintained. This differential response has promising perspectives for improved clinical outcome. This study investigates tumor control and normal tissue toxicity of pencil beam scanning (PBS) proton FLASH in a mouse model.METHODS AND MATERIALS: Tumor bearing hind limbs of non-anaesthetized CDF1 mice were irradiated in a single fraction with a PBS proton beam using either conventional (CONV) dose rate (0.33-0.63 Gy/s field dose rate, 244 MeV) or FLASH (71-89 Gy/s field dose rate, 250 MeV). 162 mice with a C3H mouse mammary carcinoma subcutaneously implanted in the foot were irradiated with physical doses of 40-60 Gy (8-14 mice per dose point). The endpoints were tumor control (TC) assessed as no recurrent tumor at 90 days after treatment, the level of acute moist desquamation (MD) to the skin of the foot within 25 days post irradiation, and radiation induced fibrosis (RIF) within 24 weeks post irradiation.RESULTS: TCD 50 (dose for 50% tumor control) was similar for CONV and FLASH with values (and 95% confidence intervals) of 49.1 (47.0-51.4) Gy for CONV and 51.3 (48.6-54.2) Gy for FLASH. RIF analysis was restricted to mice with tumor control. Both endpoints showed distinct normal tissue sparing effect of proton FLASH with MDD 50 (dose for 50% of mice displaying moist desquamation) of <40.1 Gy for CONV and 52.3 (50.0-54.6) Gy for FLASH, (dose modifying factor at least 1.3) and FD 50 (dose for 50% of mice displaying fibrosis) of 48.6 (43.2-50.8) Gy for CONV and 55.6 (52.5-60.1) Gy for FLASH (dose modifying factor of 1.14). CONCLUSIONS: FLASH had the same tumor control as CONV, but reduced normal tissue damage assessed as acute skin damage and radiation induced fibrosis.",
author = "S{\o}rensen, {Brita Singers} and Sitarz, {Mateusz Krzysztof} and Christina Ankj{\ae}rgaard and Johansen, {Jacob G} and Andersen, {Claus E} and Eleni Kanouta and Cai Grau and Per Poulsen",
note = "Copyright {\textcopyright} 2022. Published by Elsevier B.V.",
year = "2022",
month = may,
day = "17",
doi = "10.1016/j.radonc.2022.05.014",
language = "English",
journal = "Radiotherapy & Oncology",
issn = "0167-8140",
publisher = "Elsevier Ireland Ltd.",

}

RIS

TY - JOUR

T1 - Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model

AU - Sørensen, Brita Singers

AU - Sitarz, Mateusz Krzysztof

AU - Ankjærgaard, Christina

AU - Johansen, Jacob G

AU - Andersen, Claus E

AU - Kanouta, Eleni

AU - Grau, Cai

AU - Poulsen, Per

N1 - Copyright © 2022. Published by Elsevier B.V.

PY - 2022/5/17

Y1 - 2022/5/17

N2 - PURPOSE: Preclinical studies indicate a normal tissue sparing effect when ultra-high dose rate (FLASH) radiation is used, while tumor response is maintained. This differential response has promising perspectives for improved clinical outcome. This study investigates tumor control and normal tissue toxicity of pencil beam scanning (PBS) proton FLASH in a mouse model.METHODS AND MATERIALS: Tumor bearing hind limbs of non-anaesthetized CDF1 mice were irradiated in a single fraction with a PBS proton beam using either conventional (CONV) dose rate (0.33-0.63 Gy/s field dose rate, 244 MeV) or FLASH (71-89 Gy/s field dose rate, 250 MeV). 162 mice with a C3H mouse mammary carcinoma subcutaneously implanted in the foot were irradiated with physical doses of 40-60 Gy (8-14 mice per dose point). The endpoints were tumor control (TC) assessed as no recurrent tumor at 90 days after treatment, the level of acute moist desquamation (MD) to the skin of the foot within 25 days post irradiation, and radiation induced fibrosis (RIF) within 24 weeks post irradiation.RESULTS: TCD 50 (dose for 50% tumor control) was similar for CONV and FLASH with values (and 95% confidence intervals) of 49.1 (47.0-51.4) Gy for CONV and 51.3 (48.6-54.2) Gy for FLASH. RIF analysis was restricted to mice with tumor control. Both endpoints showed distinct normal tissue sparing effect of proton FLASH with MDD 50 (dose for 50% of mice displaying moist desquamation) of <40.1 Gy for CONV and 52.3 (50.0-54.6) Gy for FLASH, (dose modifying factor at least 1.3) and FD 50 (dose for 50% of mice displaying fibrosis) of 48.6 (43.2-50.8) Gy for CONV and 55.6 (52.5-60.1) Gy for FLASH (dose modifying factor of 1.14). CONCLUSIONS: FLASH had the same tumor control as CONV, but reduced normal tissue damage assessed as acute skin damage and radiation induced fibrosis.

AB - PURPOSE: Preclinical studies indicate a normal tissue sparing effect when ultra-high dose rate (FLASH) radiation is used, while tumor response is maintained. This differential response has promising perspectives for improved clinical outcome. This study investigates tumor control and normal tissue toxicity of pencil beam scanning (PBS) proton FLASH in a mouse model.METHODS AND MATERIALS: Tumor bearing hind limbs of non-anaesthetized CDF1 mice were irradiated in a single fraction with a PBS proton beam using either conventional (CONV) dose rate (0.33-0.63 Gy/s field dose rate, 244 MeV) or FLASH (71-89 Gy/s field dose rate, 250 MeV). 162 mice with a C3H mouse mammary carcinoma subcutaneously implanted in the foot were irradiated with physical doses of 40-60 Gy (8-14 mice per dose point). The endpoints were tumor control (TC) assessed as no recurrent tumor at 90 days after treatment, the level of acute moist desquamation (MD) to the skin of the foot within 25 days post irradiation, and radiation induced fibrosis (RIF) within 24 weeks post irradiation.RESULTS: TCD 50 (dose for 50% tumor control) was similar for CONV and FLASH with values (and 95% confidence intervals) of 49.1 (47.0-51.4) Gy for CONV and 51.3 (48.6-54.2) Gy for FLASH. RIF analysis was restricted to mice with tumor control. Both endpoints showed distinct normal tissue sparing effect of proton FLASH with MDD 50 (dose for 50% of mice displaying moist desquamation) of <40.1 Gy for CONV and 52.3 (50.0-54.6) Gy for FLASH, (dose modifying factor at least 1.3) and FD 50 (dose for 50% of mice displaying fibrosis) of 48.6 (43.2-50.8) Gy for CONV and 55.6 (52.5-60.1) Gy for FLASH (dose modifying factor of 1.14). CONCLUSIONS: FLASH had the same tumor control as CONV, but reduced normal tissue damage assessed as acute skin damage and radiation induced fibrosis.

U2 - 10.1016/j.radonc.2022.05.014

DO - 10.1016/j.radonc.2022.05.014

M3 - Journal article

C2 - 35595175

JO - Radiotherapy & Oncology

JF - Radiotherapy & Oncology

SN - 0167-8140

ER -