Abstract Body

FLASH radiotherapy (RT) is delivered at ultra-high dose rates (>40 Gy/s), with preclinical animal data suggesting less toxicity to normal tissues. FAST-01 was a prospective, first-in-human study that evaluated the feasibility of a clinical workflow for proton FLASH RT in the treatment of painful extremity bone metastases. The treatment workflow was hypothesized to be feasible. In addition, this study intended to generate preliminary results regarding the safety and efficacy of this FLASH treatment.
FAST-01 was a single institution study under an FDA investigational device exemption (IDE) approved for 10 patients with >2 month life expectancy and 1-3 painful bone metastases in the extremities. Exclusion criteria included patients with fractures or prior RT in the treatment site(s), or lesions of the feet, hands, or wrists. Treatment was 8 Gy (RBE = 1.0) in a single fraction delivered at ≥40 Gy/s via a FLASH-enabled proton therapy system employing a single transmission proton beam. Primary study endpoints were workflow feasibility (time on the treatment table and FLASH-related treatment delays) and toxicity, and secondary endpoint was efficacy (validated pain questionnaires). Pain flare questionnaires were completed for 10 consecutive days post-RT. Pain response at each treatment site was evaluated at 3 months post-RT using the methodology of RTOG 9714. Pain, pain medication use, and adverse events (AEs) were evaluated on the day of treatment and at 15 days, 1, 2, and 3 months post-RT, and every 2 months thereafter. AEs were graded using CTCAE v5. Safety analysis included all events that were physician-attributed to be at least “possibly related” to FLASH. Photos of skin in the treatment site areas supported AE evaluations.
Ten subjects aged 27-81 years received FLASH RT to 12 metastatic sites. No FLASH-related technical issues or delays occurred. Average time on the treatment table was 15.8 min per treated site (range 11-33 min). Follow-up ranged from 2.3-13 months (median 4.8 months). Transient pain flares occurred in 4 of 12 treated sites. Complete or partial pain relief following FLASH radiotherapy was seen in 8 of 12 sites (7 of the 10 subjects) for an overall response rate of 66.7%. Complete pain responses were 50% (6/12 sites), and partial responses were 17% (2/12 sites). AEs were mild: skin hyperpigmentation (G1, n=4), skin discoloration (G1, n=1), limb edema (G1, n=2), pruritis (G1, n=2), fatigue (G1, n=1), erythema (G1, n=1), and extremity pain (G2, n=1).
This first-in-human trial establishes the feasibility of FLASH proton radiotherapy. The treatment efficacy and the profile of AEs were favorable and were comparable to the published literature for conventional dose rate photon RT. AE and pain data collection continues for the evaluation of long-term results. These findings support the further exploration of FLASH radiation treatments for other clinical indications.