Moderator of 1 Session
Presenter of 3 Presentations
Q&A
Clinical Evidence Strategy - FAST-01 & beyond
Translation of Proton FLASH to Clinical Trials: The FAST Roadmap
Abstract
Abstract Body
Radiotherapy plays an essential role in the treatment of more than half of all cancer patients. FLASH radiotherapy (FLASH-RT) delivers radiation treatment at ultra-high dose rates that are several orders of magnitude higher than current clinical practice. In multiple pre-clinical studies in different model systems, FLASH-RT has demonstrated consistent normal tissue sparing effects while preserving equivalent anti-tumor activity in comparison to conventional dose rate radiation treatment. In this talk, I will outline how such normal tissue sparing could address important clinical needs and I will describe Varian’s approach to addressing these clinical questions in a rational sequence of clinical trials. Varian’s FAST-01 was the first clinical trial to study proton FLASH in patients with cancer. Following demonstration of feasibility and safety in the FAST-01 and FAST-02 clinical trials of palliative FLASH-RT for bone metastases, clinical trials of definitive dose RT will be required to establish the future clinical role of FLASH-RT. In this talk, I will discuss regulatory and clinical aspects of these future trials.Author Of 4 Presentations
Clinical Evidence Strategy - FAST-01 & beyond
Q&A
Translation of Proton FLASH to Clinical Trials: The FAST Roadmap
Abstract
Abstract Body
Radiotherapy plays an essential role in the treatment of more than half of all cancer patients. FLASH radiotherapy (FLASH-RT) delivers radiation treatment at ultra-high dose rates that are several orders of magnitude higher than current clinical practice. In multiple pre-clinical studies in different model systems, FLASH-RT has demonstrated consistent normal tissue sparing effects while preserving equivalent anti-tumor activity in comparison to conventional dose rate radiation treatment. In this talk, I will outline how such normal tissue sparing could address important clinical needs and I will describe Varian’s approach to addressing these clinical questions in a rational sequence of clinical trials. Varian’s FAST-01 was the first clinical trial to study proton FLASH in patients with cancer. Following demonstration of feasibility and safety in the FAST-01 and FAST-02 clinical trials of palliative FLASH-RT for bone metastases, clinical trials of definitive dose RT will be required to establish the future clinical role of FLASH-RT. In this talk, I will discuss regulatory and clinical aspects of these future trials.FLASH PROTON PENCIL BEAM SCANNING IRRADIATION USING A CLINICAL GANTRY DIMINISHES RADIATION INDUCED SKIN AND SOFT TISSUE TOXICITY IN MICE
Abstract
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.