FAST-02: Results from the second in-human prospective evaluation of single-fraction proton FLASH for symptomatic...

FAST-01 demonstrated that proton FLASH radiotherapy (FLASH-RT) is clinically feasible and has an acceptable safety profile in patients with painful bone metastases of the extremities. FAST-02 expanded the investigation of FLASH-RT to patients whose treatment sites lie closer to critical normal structures.

FAST-02 was a prospective, single-arm clinical trial (FDA IDE G220086) in which adult patients with 1-3 painful non-vertebral thoracic bone metastases were treated with FLASH-RT (8 Gy, ≥40 Gy/second). The co-primary objectives of FAST-02 were patient-reported toxicity and efficacy of pain relief. The trial's secondary objective was to evaluate FLASH-RT workflow metrics. Patients reported adverse events as well as overall pain, treatment site pain, and pain flare. Time-on-table and device-related treatment malfunctions were recorded.

Twelve patients were enrolled, and 10 patients were treated with FLASH-RT. Histologic diagnoses spanned lung, prostate, and kidney cancers. One site was treated per patient in the rib or scapula. All patients completed treatment per protocol. Average time-on-table was 14.6 min. At a median follow-up of 189 days, there were no ≥ grade 2 acute or late adverse events at least possibly related to FLASH-RT. Three-month pain was available in 8 patients; 1-month pain was available in 2 patients. A complete response was observed in 6 patients, a partial response in 3 patients, and stable response in 1 patient. Three patients reported pain flares by day 11 of follow-up.

FAST-02, the first prospective clinical study of FLASH adjacent to thoracic critical organs, supported that FLASH-RT can be effective and has an acceptable safety profile in study patients with painful thoracic bony metastases.