Xstrahl in Action
Studies during the past 9 years suggest that delivering radiation at dose rates exceeding 40 Gy/s, known as “FLASH” radiation therapy, enhances the therapeutic index of radiation therapy (RT) by decreasing normal tissue damage while maintaining tumor response compared with conventional (or standard) RT. This study demonstrates the cardioprotective benefits of FLASH proton RT (F-PRT) compared with standard (conventional) proton RT (S-PRT), as evidenced by reduced acute and chronic cardiac toxicities. This study demonstrated that FLASH proton RT (F-PRT) reduces the induction of an inflammatory environment with lower expression of inflammatory cytokines and profibrotic factors. Importantly, the results indicate that F-PRT better preserves cardiac functionality, as confirmed by echocardiography analysis, while also mitigating the development of long-term fibrosis.
Publication
FLASH Proton Radiation Therapy Mitigates Inflammatory and Fibrotic Pathways and Preserves Cardiac Function in a Preclinical Mouse Model of Radiation-Induced Heart Disease
Authors
Kyle Kim BS, Michele M. Kim PhD, Giorgos Skoufos PhD, Eric S. Diffenderfer PhD, Seyyedeh Azar Oliaei Motlagh PhD, Michail Kokkorakis BS, Ilektra Koliaki BS, George Morcos BS, Khayrullo Shoniyozov PhD, Joanna Griffin MS, et al.
Key Findings
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No deaths or skin toxicities were recorded during or at any timepoint post-PRT in any of the treatment schemes and modalities, and all mice remained healthy after RT.
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Compared with the S-PRT treated hearts, the F-PRT focally irradiated hearts preserved many crucial parameters, including LVIDd, LV mass, ejection time, and relative wall thickness, with levels closely resembling those of nonirradiated mice.
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F-PRT mitigates late-stage RIHD (primarily fibrosis) and preserves cardiac functionality compared with S-PRT.
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It was demonstrated that F-PRT spares cardiac apex from both acute and chronic toxicities compared with S-PRT.
The Value of SARRP
Using the Small Animal Radiation Research Platform (SARRP), mice randomly assigned to treatment groups underwent image guided RT and were irradiated with a single dose of 40 Gy of S-PRT or F-PRT at the cardiac apex with a 5-mm diameter circular collimator. Using the SARRP’s Control Interface, contrast-enhanced cone beam computed tomography images were initiated and an RT plan was designed accordingly (Fig. 1b)
Figure 1. Irradiation setup. (a) Irradiation setting; the proton beam angled at 15° to the vertical (created with BioRender.com). (b) Dose plan in MuriPlan. Frontal view of RT planning and delivery to the cardiac apex at a dose of 40 Gy with a 5-mm diameter circular collimator angled at 15° to the horizontal. Purple and orange areas indicate the unirradiated and irradiated cardiac areas, respectively. (c) Timeline of experiments conducted in this study. (d) phosphorylated form of histone H2AX immunofluorescence staining in optimal cutting temperature-frozen FLASH proton RT or standard (conventional) proton RT-treated cardiac sections. The red dotted circle outlines the irradiated area. Scale bar, 1 mm. Abbreviation: RT = radiation therapy.
