Demonstration of the FLASH Effect Within the Spread-out Bragg Peak After Abdominal Irradiation of Mice

Abstract Purpose The effects of FLASH-level dose rates delivered at the spread-out Bragg peak (SOBP) on normal tissue damage in mice were investigated. Materials and Methods Fifty nontumor-bearing mice received abdominal irradiation, 30 at FLASH dose rates (100 Gy/s) and 20 at conventional dose rates (0.1 Gy/s). Total dose values ranged from 10 to 19 Gy, delivered in a single spot by a synchrocyclotron proton therapy system. Centered on the abdomen, the collimated field delivered was an 11-mm diameter circle with a water-equivalent depth of 2.4 cm from entrance to distal 80% dose. A ridge filter was used to provide dose uniformity over the full 2.4-cm range. The spatial distribution was identical for both the FLASH and conventional deliveries. Results Overall survival and individual mouse weights were tracked for 21 days after the exposure date, and LD50 values were compared for the FLASH and conventional dose rate groups. Mice exposed to FLASH dose rates had a higher LD50 value as compared with mice exposed to conventional dose rates, with a dose-dependent improvement in survivability of 10% to 20%. The FLASH cohort also showed greater or equal percent population survival for each day of the study. Conclusion These results are preliminary confirmation of the potential for the combination of the advantages of the Bragg peak with the normal tissue sparing benefits of FLASH treatments. This experiment also confirms that pulsed synchrocyclotrons can be used for the purpose of FLASH research and treatment.

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(P003) Delivery of Ultra-Rapid Flash Radiation Therapy and Demonstration of Normal Tissue Sparing After Abdominal Irradiation of Mice

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2017.02.101 ◽

2017 ◽

Vol 98 (2) ◽

pp. E16 ◽

Cited By ~ 38

Author(s):

Billy W. Loo ◽

Emil Schuler ◽

Frederick M. Lartey ◽

Marjan Rafat ◽

Gregory J. King ◽

...

Keyword(s):

Radiation Therapy ◽

Normal Tissue ◽

Normal Tissue Sparing ◽

Tissue Sparing ◽

Abdominal Irradiation

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Comparison of the predictions of the LQ and CRE models for normal tissue damage due to biologically targeted radiotherapy with exponentially decaying dose rates

Radiotherapy and Oncology ◽

10.1016/0167-8140(89)90082-0 ◽

1989 ◽

Vol 15 (4) ◽

pp. 359-362 ◽

Cited By ~ 4

Author(s):

J.A. O'Donoghue

Keyword(s):

Tissue Damage ◽

Normal Tissue ◽

Targeted Radiotherapy ◽

Dose Rates ◽

Normal Tissue Damage

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Unexpected Benefits of Multiport Synchrotron Microbeam Radiation Therapy for Brain Tumors

Cancers ◽

10.3390/cancers13050936 ◽

2021 ◽

Vol 13 (5) ◽

pp. 936

Author(s):

Laura Eling ◽

Audrey Bouchet ◽

Alexandre Ocadiz ◽

Jean-François Adam ◽

Sarvenaz Kershmiri ◽

...

Keyword(s):

Radiation Therapy ◽

Brain Tumors ◽

Normal Tissue ◽

Therapeutic Index ◽

Tumor Control ◽

Microbeam Radiation Therapy ◽

Normal Tissue Damage ◽

Tissue Sparing ◽

Extended Survival ◽

Better Than

Delivery of high-radiation doses to brain tumors via multiple arrays of synchrotron X-ray microbeams permits huge therapeutic advantages. Brain tumor (9LGS)-bearing and normal rats were irradiated using a conventional, homogeneous Broad Beam (BB), or Microbeam Radiation Therapy (MRT), then studied by behavioral tests, MRI, and histopathology. A valley dose of 10 Gy deposited between microbeams, delivered by a single port, improved tumor control and median survival time of tumor-bearing rats better than a BB isodose. An increased number of ports and an accumulated valley dose maintained at 10 Gy delayed tumor growth and improved survival. Histopathologically, cell death, vascular damage, and inflammatory response increased in tumors. At identical valley isodose, each additional MRT port extended survival, resulting in an exponential correlation between port numbers and animal lifespan (r2 = 0.9928). A 10 Gy valley dose, in MRT mode, delivered through 5 ports, achieved the same survival as a 25 Gy BB irradiation because of tumor dose hot spots created by intersecting microbeams. Conversely, normal tissue damage remained minimal in all the single converging extratumoral arrays. Multiport MRT reached exceptional ~2.5-fold biological equivalent tumor doses. The unique normal tissue sparing and therapeutic index are eminent prerequisites for clinical translation.

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Comparison of FLASH Proton Entrance and the Spread-Out Bragg Peak Dose Regions in the Sparing of Mouse Intestinal Crypts and in a Pancreatic Tumor Model

Cancers ◽

10.3390/cancers13164244 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4244

Author(s):

Michele M. Kim ◽

Ioannis I. Verginadis ◽

Denisa Goia ◽

Allison Haertter ◽

Khayrullo Shoniyozov ◽

...

Keyword(s):

Dose Rate ◽

Bragg Peak ◽

Standard Dose ◽

Biological Effects ◽

Entrance Region ◽

Treatment Modalities ◽

High Dose ◽

Proton Radiotherapy ◽

Dose Rates ◽

Spread Out Bragg Peak

Ultra-high dose rate FLASH proton radiotherapy (F-PRT) has been shown to reduce normal tissue toxicity compared to standard dose rate proton radiotherapy (S-PRT) in experiments using the entrance portion of the proton depth dose profile, while proton therapy uses a spread-out Bragg peak (SOBP) with unknown effects on FLASH toxicity sparing. To investigate, the biological effects of F-PRT using an SOBP and the entrance region were compared to S-PRT in mouse intestine. In this study, 8–10-week-old C57BL/6J mice underwent 15 Gy (absorbed dose) whole abdomen irradiation in four groups: (1) SOBP F-PRT, (2) SOBP S-PRT, (3) entrance F-PRT, and (4) entrance S-PRT. Mice were injected with EdU 3.5 days after irradiation, and jejunum segments were harvested and preserved. EdU-positive proliferating cells and regenerated intestinal crypts were quantified. The SOBP had a modulation (width) of 2.5 cm from the proximal to distal 90%. Dose rates with a SOBP for F-PRT or S-PRT were 108.2 ± 8.3 Gy/s or 0.82 ± 0.14 Gy/s, respectively. In the entrance region, dose rates were 107.1 ± 15.2 Gy/s and 0.83 ± 0.19 Gy/s, respectively. Both entrance and SOBP F-PRT preserved a significantly higher number of EdU + /crypt cells and percentage of regenerated crypts compared to S-PRT. Moreover, tumor growth studies showed no difference between SOBP and entrance for either of the treatment modalities.

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