Effects of whole brain proton irradiation at conventional or ultra-high dose rate (FLASH), in adult male Sprague Dawley rats.

in Scientific reports by Michael T Williams, Samantha L Regan, Adam L Fritz, Brooke M Gollaway, Anthony E Mascia, Ralph E Vatner, John P Perentesis, Charles V Vorhees

TLDR

  • The study found that FLASH treatment after cranial proton irradiation did not reduce cognitive toxicity in rats, suggesting that alternative approaches may be needed to mitigate cognitive side effects.

Abstract

Radiation is an effective treatment for many brain tumors, but often causes cognitive impairment. Ultra-high dose rate (FLASH) radiotherapy is less toxic to many normal tissues and may protect against adverse cognitive effects of cranial irradiation. Adult male Sprague Dawley rats received a single 18 Gy fraction of cranial irradiation with protons at 1 Gy/s (CV), 60 Gy/s (FLASH-60), 95 Gy/s (FLASH-95), or sham treatment (Control) (n ≥ 22/group). Rats were tested in open-field, acoustic (ASR) and tactile startle (TSR), novelty preference, radial water maze (RWM), Morris water maze (MWM), Cincinnati water maze configurations A and B (CWM-A CWM-B), and novelty tests. Locomotion was decreased and TSR increased in all irradiated rats and ASR increased in FLASH-95 rats compared with Controls. In MWM acquisition and reversal, the CV and FLASH-60 rats had reduced path efficiency but during shift and shift reversal all irradiated rats had increased latencies and reduced path efficiencies compared with Controls. In CWM-A all irradiated rats performed below Controls. There were no differences found in CWM-B, novelty tests, or RWM. In summary, FLASH treatment after 18 Gy cranial proton irradiation did not result in reduced cognitive toxicity.

Overview

  • The study investigates the effectiveness of ultra-high dose rate (FLASH) radiotherapy in reducing cognitive impairment caused by cranial irradiation in adult male rats.
  • The study uses a single 18 Gy fraction of cranial irradiation with protons at different dose rates (1 Gy/s, 60 Gy/s, and 95 Gy/s) and compares the results with sham-treated control group.
  • The primary objective is to determine if FLASH treatment after cranial proton irradiation can reduce cognitive toxicity in rats.

Comparative Analysis & Findings

  • The results show that all irradiated rats exhibited decreased locomotion, increased tactile startle response, and altered performance in various cognitive tests compared to the control group.
  • FLASH-95 rats showed increased acoustic startle response compared to controls, while CV and FLASH-60 rats demonstrated reduced path efficiency in Morris water maze acquisition and reversal.
  • The study found no differences in Cincinnati water maze performance, novelty tests, or radial water maze between irradiated and control groups.

Implications and Future Directions

  • The study suggests that FLASH treatment after 18 Gy cranial proton irradiation did not result in reduced cognitive toxicity, which may have implications for the treatment of brain tumors in humans.
  • Future studies should investigate optimal FLASH dose rates and treatment regimens to minimize cognitive side effects.
  • Additionally, studies should explore the use of FLASH radiotherapy in combination with other treatments to enhance its efficacy and reduce toxicity.
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