Feasibility Study of FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases

Toxicities that are possibly, probably, or definitely related to FLASH radiotherapy. Toxicities will be classified per CTCAE version 5.0. The outcome measure data table summarizes the total number of adverse events possibly, probably, definitely related to treatment that were reported in the 10 participant cohort. Eleven adverse events were grade 1 and one adverse event was grade 2, as classified by CTCAE version 5.0.

Time frame: Assessed from start of treatment until subject death or lost to follow-up, up to 17.8 months

Number of participants with total time on table under one hour. The investigational site staff will measure the time for participant set-up and positioning on the treatment couch, imaging and FLASH treatment delivery. The workflow feasibility outcome measure is met for an individual subject if total time on table is measured as less than one hour. The outcome measure data table provides the mean and full range of time on table (as measured in minutes) for the 10 participants. The participant with a treatment time of 33 minutes received treatment to two separate metastatic sites; remaining 9 participants received treatment to a single metastatic site.

Time frame: Will be assessed on day of treatment delivery which occurs within 3 weeks of subject enrollment.

Number of participants whose treatment was delayed by more than 7 business days from simulation to treatment when related to the investigational device (excluding delays due to patient or facility factors not related to study treatment). The investigational site staff will measure the number of days delay in time to treatment due to problems involving the investigational device. The workflow feasibility outcome measure is met for an individual subject if the delay is measured as less than 7 days. The outcome measure data table provides the mean and full range days of treatment delay for the 10 participants.

Time frame: Will be assessed within 4 weeks of subject enrollment.

Pain was assessed by patient reported validated 10 point pain flare questionnaire. Pain flare is defined as either of the following: A) a minimum of a two-point increase in the worst pain score for the treated site without a reduction in analgesic intake; or B) a 25% or greater increase in analgesic intake based on daily oral morphine equivalence without a reduction in the worst pain score.

Time frame: First 10 days post FLASH treatment

Use of pain medication by study participant during days 1-10 following FLASH treatment was collected as it constituted one of the defining criteria (criteria B) for the pain flare outcome measure. Pain flare is defined as either of the following: A) a minimum of a two-point increase in the worst pain score for the treated site without a reduction in analgesic intake; or B) a 25% or greater increase in analgesic intake based on daily oral morphine equivalence without a reduction in the worst pain score.

Time frame: Within 10 days after treatment.

Population: Four out of the 10 participants experienced a pain flare. Two of these 4 participants met criteria B) whose use of pain medication in the first 10 days after treatment met the endpoint for pain flare.

Percentage of treated sites achieving pain relief as measured using patient reported outcome questionnaires (Brief Pain Inventory Questionnaire, Treated Sites Pain Questionnaire). Categories of pain relief included complete, partial, stable or progressive response. Complete response (CR) = no pain at 3 months Partial response (PR) = an average pain score that is ≥2 points lower than initial Stable disease (SD) = an average pain score that is ±1 point change from initial Progressive disease (PD) = an average pain score that is ≥2 points higher than initial

Time frame: At 3 month follow up

Population: The outcome measures data table details the percentage of pain response rate (in the categories of response described above) for 12 treated sites involving 10 participants.