Ultra-high dose-rate proton FLASH improves tumor control

Radiother Oncol. 2023 Sep:186:109741. doi: 10.1016/j.radonc.2023.109741. Epub 2023 Jun 12.

Abstract

Background and purpose: Proton radiotherapy (PRT) offers potential benefits over other radiation modalities, including photon and electron radiotherapy. Increasing the rate at which proton radiation is delivered may provide a therapeutic advantage. Here, we compared the efficacy of conventional proton therapy (CONVpr) to ultrahigh dose-rate proton therapy, FLASHpr, in a mouse model of non-small cell lung cancers (NSCLC).

Materials and methods: Mice bearing orthotopic lung tumors received thoracic radiation therapy using CONVpr (<0.05 Gy/s) and FLASHpr (>60 Gy/s) dose rates.

Results: Compared to CONVpr, FLASHpr was more effective in reducing tumor burden and decreasing tumor cell proliferation. Furthermore, FLASHpr was more efficient in increasing the infiltration of cytotoxic CD8+ T-lymphocytes inside the tumor while simultaneously reducing the percentage of immunosuppressive regulatory T-cells (Tregs) among T-lymphocytes. Also, compared to CONVpr, FLASHpr was more effective in decreasing pro-tumorigenic M2-like macrophages in lung tumors, while increasing infiltration of anti-tumor M1-like macrophages. Finally, FLASHpr treatment reduced expression of checkpoint inhibitors in lung tumors, indicating reduced immune tolerance.

Conclusions: Our results suggest that FLASH dose-rate proton delivery modulates the immune system to improve tumor control and might thus be a promising new alternative to conventional dose rates for NSCLC treatment.

Keywords: FLASH; Lung cancer; Mouse model; Proton radiotherapy; Ultrahigh dose-rate proton.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Lung Neoplasms* / radiotherapy
  • Mice
  • Proton Therapy* / methods
  • Protons
  • Radiotherapy Dosage

Substances

  • Protons