Background and Aims

The FLASH effect occurs in tissue when therapeutic radiation dose is delivered at ultra-high dose-rates (UHDR), greater than 40 Gy/s. At these dose-rates, the probability of sparing healthy tissue is greatly enhanced whilst damage to cancerous tissue remains devastating. In the clinic, accurate determination of absorbed-dose delivered to the target region at UHDR is challenging due to inefficient collection of charge within ionisation chambers (IC), and over-response of radiochromic film (RCF).

National Physical Laboratory (NPL), scientists re-purposed a simple portable graphite calorimeter (SPGC), for use with UHDR particle beams.

Methods

Measurements were carried out using a clinical 250 MeV scanned-proton beam system adapted to deliver FLASH proton radiotherapy beams and compared with the NPL primary-standard level graphite proton calorimeter, IC, RCF and alanine pellets, all in terms of dose-to-water.

Results

Preliminary analysis indicates agreement between the SPGC and primary-standard level calorimeter is within the overall combined measurement uncertainties of 1.5%, k=1. Calculation of calorimeter perturbation factors using Monte Carlo simulations are ongoing, as well as analysis of RCF, IC and alanine data.

Conclusions

This presentation will explain the measurement protocol carried out, present the results obtained and the associated levels of measurement uncertainty to show how a simple, portable calorimeter can be an effective tool in the clinic to accurately determine absorbed-dose delivered to the target at a significantly lower value of measurement uncertainty than current IC measurement protocols, typically >2%, k=1, or to determine correction factors for IC and RCF measurements in the clinic.

This project was funded by EMPIR 18HLT04UHDpulse

Background and Aims

Radiation induced skin and soft tissue toxicity remains a complication even for targeted proton pencil beam scanning (PBS) therapy. In this study, we determined the feasibility and benefit of Flash PBS therapy on these toxicities in mice.

Methods

A uniform dose of 35 Gy (toxicity study) or 15 Gy (tumor control study) was delivered to the right hind leg of mice at 1 Gy/s (Conv), 57 Gy/s (FLASH60) and 115 Gy/s (FLASH115) using the plateau region of a 250MeV proton beam. Acute radiation effects were quantified by measurements of TGF-β1 in the plasma and skin and by skin toxicity scoring. Delayed irradiation response was defined by hind leg contracture and plasma levels of 13 cytokines (CXCL1, CXCL10, Eotaxin, IL1-beta, IL-6, MCP-1, Mip1alpha, TNF-alpha, TNF-beta, VEGF, G-CSF, GM-CSF and TGF-β1). Tumor control was quantified in vivo using MOC1 and MOC2 murine oral squamous cell carcinoma (OSCC) cells transplanted into the flank of immunocompetent mice.

Results

Plasma and skin levels of TGF-β1, skin toxicity and leg contracture were significantly decreased in FLASH compared to Conv groups. Maximal FLASH effect was already observed at 60 Gy/s. Plasma levels of CXCL1, GM-CSF, G-CSF and IL-6 were significantly different between FLASH and Con PBS treated animals. FLASH and Conv PBS had similar efficacy on MOC1 and MOC2 tumor growth in vivo.

Conclusions

FLASH PBS radiation can be delivered to mice at dose rates up to 115 Gy/s in a clinical gantry and can improve radiation induced skin and soft tissue toxicity while remaining isoefficient in delaying OSCC growth.