プロスペクティブ第I相「フラッシュスキンI」試験：臨床リニアックにおける超高線量率放射線療法の実施と品質保証

The combination of reduced normal tissue damage and unaffected tumor control is referred to as Flash-effect. This phenomenon has been observed with ultra-high dose rate (UHDR) radiotherapy in preclinical models. The Flash-Skin I (NCT06549439) treated seven patients with melanoma skin metastasis. The treatment protocol included 2 × 9 Gy UHDR followed by 1 × 9 Gy conventional radiotherapy. Here we report on the implementation of the study at a converted C-arm clinical linear accelerator.

A dedicated preclinical radiation therapy quality assurance (RTQA) program was developed and the linac performance was validated for more than one year. Clinically, fourteen fractions of 9 Gy each were delivered with the 9 MeV UHDR electron linac. In-vivo measurements included: skin dose with radiochromic films, linac output with optically stimulated luminescent dosimeter (OSLD), pulse counting and inter-pulse stability with a scintillator, intra-pulse stability with a diamond detector.

The preclinical RTQA identified reduced linac output, which prompted beam tuning and additional quality assurance. This formed the basis for initiation of the clinical trial and successful treatment of all seven patients. All fourteen UHDR fractions showed a dose accuracy within 4.6% or better. The number of delivered pulses consistently matched the planned value, and film measurements confirmed the skin dose. Intra- and inter-pulse stability were within 3.8% and 2.8%, respectively.

The clinical implementation of Flash-Skin I at converted C-arm linac was successfully demonstrated and validated. The developed RTQA program may facilitate the development of future UHDR clinical trials.