{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:49:32Z","timestamp":1793911772621,"version":"4.8.0"},"reference-count":21,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"Importance<\/jats:title>To our knowledge, there have been no clinical trials of ultra-high-dose-rate radiotherapy delivered at more than 40 Gy\/sec, known as FLASH therapy, nor first-in-human use of proton FLASH.<\/jats:p><\/jats:sec>Objectives<\/jats:title>To assess the clinical workflow feasibility and treatment-related toxic effects of FLASH and pain relief at the treatment sites.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>In the FAST-01 nonrandomized trial, participants treated at Cincinnati Children\u2019s\/UC Health Proton Therapy Center underwent palliative FLASH radiotherapy to extremity bone metastases. Patients 18 years and older with 1 to 3 painful extremity bone metastases and life expectancies of 2 months or more were eligible. Patients were excluded if they had foot, hand, and wrist metastases; metastases locally treated in the 2 weeks prior; metal implants in the treatment field; known enhanced tissue radiosensitivity; and implanted devices at risk of malfunction with radiotherapy. One of 11 patients who consented was excluded based on eligibility. The end points were evaluated at 3 months posttreatment, and patients were followed up through death or loss to follow-up for toxic effects and pain assessments. Of the 10 included patients, 2 died after the 2-month follow-up but before the 3-month follow-up; 8 participants completed the 3-month evaluation. Data were collected from November 3, 2020, to January 28, 2022, and analyzed from January 28, 2022, to September 1, 2022.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Bone metastases were treated on a FLASH-enabled (\u226540 Gy\/sec) proton radiotherapy system using a single-transmission proton beam. This is consistent with standard of care using the same prescription (8 Gy in a single fraction) but on a conventional-dose-rate (approximately 0.03 Gy\/sec) photon radiotherapy system.<\/jats:p><\/jats:sec>Main Outcome and Measures<\/jats:title>Main outcomes included patient time on the treatment couch, device-related treatment delays, adverse events related to FLASH, patient-reported pain scores, and analgesic use.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 10 patients (age range, 27-81 years [median age, 63 years]; 5 [50%] male) underwent FLASH radiotherapy at 12 metastatic sites. There were no FLASH-related technical issues or delays. The average (range) time on the treatment couch was 18.9 (11-33) minutes per patient and 15.8 (11-22) minutes per treatment site. Median (range) follow-up was 4.8 (2.3-13.0) months. Adverse events were mild and consistent with conventional radiotherapy. Transient pain flares occurred in 4 of the 12 treated sites (33%). In 8 of the 12 sites (67%) patients reported pain relief, and in 6 of the 12 sites (50%) patients reported a complete response (no pain).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this nonrandomized trial, clinical workflow metrics, treatment efficacy, and safety data demonstrated that ultra-high-dose-rate proton FLASH radiotherapy was clinically feasible. The treatment efficacy and the profile of adverse events were comparable with those of standard-of-care radiotherapy. These findings support the further exploration of FLASH radiotherapy in patients with cancer.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04592887<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.5843","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T15:30:32Z","timestamp":1666539032000},"page":"62","source":"Crossref","is-referenced-by-count":358,"title":["Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases"],"prefix":"10.1001","volume":"9","author":[{"given":"Anthony E.","family":"Mascia","sequence":"first","affiliation":[{"name":"Cancer and Blood Diseases Institute, Cincinnati Children\u2019s Hospital, Cincinnati, Ohio"},{"name":"Department of Radiation Oncology, College of Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily 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