{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:03:34Z","timestamp":1792263814868,"version":"4.4.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Varian, a Siemens Healthineers Company"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Radiat Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      FLASH therapy is a treatment technique in which radiation is delivered at ultra-high dose rates (\n                      <jats:underline>\u2265<\/jats:underline>\n                      \u200940\u00a0Gy\/s). The first-in-human FAST-01 clinical trial demonstrated the clinical feasibility of proton FLASH in the treatment of extremity bone metastases. The objectives of this investigation are to assess the toxicities of treatment and pain relief in study participants with painful thoracic bone metastases treated with FLASH radiotherapy, as well as workflow metrics in a clinical setting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-arm clinical trial is being conducted under an FDA investigational device exemption (IDE) approved for 10 patients with 1\u20133 painful bone metastases in the thorax, excluding bone metastases in the spine. Treatment will be 8\u00a0Gy in a single fraction administered at \u2265\u200940\u00a0Gy\/s on a FLASH-enabled proton therapy system delivering a single transmission proton beam. Primary study endpoints are efficacy (pain relief) and safety. Patient questionnaires evaluating pain flare at the treatment site will be completed for 10 consecutive days post-RT. Pain response and adverse events (AEs) will be evaluated on the day of treatment and on day 7, day 15, months 1, 2, 3, 6, 9, and 12, and every 6 months thereafter. The outcomes for clinical workflow feasibility are the occurrence of any device issues as well as time on the treatment table.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This prospective clinical trial will provide clinical data for evaluating the efficacy and safety of proton FLASH for palliation of bony metastases in the thorax. Positive findings will support the further exploration of FLASH radiation for other clinical indications including patient populations treated with curative intent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT05524064.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13014-024-02419-4","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T17:22:47Z","timestamp":1710264167000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["FLASH radiotherapy for the treatment of symptomatic bone metastases in the thorax (FAST-02): protocol for a prospective study of a novel radiotherapy approach"],"prefix":"10.1186","volume":"19","author":[{"given":"EC","family":"Daugherty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AE","family":"Mascia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Sertorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"McCann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KJ","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RA","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Khuntia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JD","family":"Bradley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"2nd","given":"CB","family":"Simone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JC","family":"Breneman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JP","family":"Perentesis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"issue":"6","key":"2419_CR1","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1158\/1078-0432.CCR-19-1440","volume":"26","author":"C Fouillade","year":"2020","unstructured":"Fouillade C, Curras-Alonso S, Giuranno L, Quelennec E, Heinrich S, Bonnet-Boissinot S, et al. FLASH irradiation spares lung progenitor cells and limits the incidence of radio-induced senescence. Clin Cancer Res. 2020;26(6):1497\u2013506.","journal-title":"Clin Cancer Res"},{"issue":"245","key":"2419_CR2","doi-asserted-by":"publisher","first-page":"245ra93","DOI":"10.1126\/scitranslmed.3008973","volume":"6","author":"V Favaudon","year":"2014","unstructured":"Favaudon V, Caplier L, Monceau V, Pouzoulet F, Sayarath M, Fouillade C, et al. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice. Sci Transl Med. 2014;6(245):245ra93.","journal-title":"Sci Transl Med"},{"issue":"3","key":"2419_CR3","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.radonc.2017.05.003","volume":"124","author":"P Montay-Gruel","year":"2017","unstructured":"Montay-Gruel P, Petersson K, Jaccard M, Boivin G, Germond JF, Petit B, et al. Irradiation in a flash: unique sparing of memory in mice after whole brain irradiation with dose rates above 100Gy\/s. Radiother Oncol. 2017;124(3):365\u20139.","journal-title":"Radiother Oncol"},{"key":"2419_CR4","doi-asserted-by":"publisher","first-page":"E16","DOI":"10.1016\/j.ijrobp.2017.02.101","volume":"98","author":"B Loo","year":"2017","unstructured":"Loo B, Schuler E, Lartey F, Rafat M, King GJ, Trovati S, et al. Delivery of Ultra-rapid Flash Radiation Therapy and demonstration of normal tissue sparing after abdominal irradiation of mice. Int J Radiat Oncol Biol Phys. 2017;98:E16.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"3","key":"2419_CR5","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1080\/09553007414551221","volume":"26","author":"SB Field","year":"1974","unstructured":"Field SB, Bewley DK. Effects of dose-rate on the radiation response of rat skin. Int J Radiat Biol Relat Stud Phys Chem Med. 1974;26(3):259\u201367.","journal-title":"Int J Radiat Biol Relat Stud Phys Chem Med"},{"issue":"1","key":"2419_CR6","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1158\/1078-0432.CCR-17-3375","volume":"25","author":"MC Vozenin","year":"2019","unstructured":"Vozenin MC, De Fornel P, Petersson K, Favaudon V, Jaccard M, Germond JF, et al. The advantage of FLASH Radiotherapy confirmed in mini-pig and cat-cancer patients. Clin Cancer Res. 2019;25(1):35\u201342.","journal-title":"Clin Cancer Res"},{"issue":"22","key":"2419_CR7","doi-asserted-by":"publisher","first-page":"10943","DOI":"10.1073\/pnas.1901777116","volume":"116","author":"P Montay-Gruel","year":"2019","unstructured":"Montay-Gruel P, Acharya MM, Petersson K, Alikhani L, Yakkala C, Allen BD, et al. Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species. Proc Natl Acad Sci USA. 2019;116(22):10943\u201351.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2419_CR8","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.radonc.2019.06.019","volume":"139","author":"J Bourhis","year":"2019","unstructured":"Bourhis J, Sozzi WJ, Jorge PG, Gaide O, Bailat C, Duclos F, et al. Treatment of a first patient with FLASH-radiotherapy. Radiotherapy Oncology: J Eur Soc Therapeutic Radiol Oncol. 2019;139:18\u201322.","journal-title":"Radiotherapy Oncology: J Eur Soc Therapeutic Radiol Oncol"},{"key":"2419_CR9","doi-asserted-by":"publisher","first-page":"e41812","DOI":"10.2196\/41812","volume":"12","author":"EC Daugherty","year":"2023","unstructured":"Daugherty EC, Mascia A, Zhang Y, Lee E, Xiao Z, Sertorio M, et al. FLASH Radiotherapy for the treatment of symptomatic bone metastases (FAST-01): protocol for the first prospective feasibility study. JMIR Res Protoc. 2023;12:e41812.","journal-title":"JMIR Res Protoc"},{"issue":"11","key":"2419_CR10","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1093\/jnci\/dji139","volume":"97","author":"WF Hartsell","year":"2005","unstructured":"Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA 3rd. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005;97(11):798\u2013804.","journal-title":"J Natl Cancer Inst"},{"issue":"1","key":"2419_CR11","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1001\/jamaoncol.2022.5843","volume":"9","author":"AE Mascia","year":"2023","unstructured":"Mascia AE, Daugherty EC, Zhang Y, Lee E, Xiao Z, Sertorio M, et al. Proton FLASH Radiotherapy for the treatment of symptomatic bone metastases: the FAST-01 Nonrandomized Trial. JAMA Oncol. 2023;9(1):62\u20139.","journal-title":"JAMA Oncol"},{"issue":"2","key":"2419_CR12","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.radonc.2008.05.018","volume":"89","author":"P Foro Arnalot","year":"2008","unstructured":"Foro Arnalot P, Fontanals AV, Galcer\u00e1n JC, Lynd F, Latiesas XS, de Dios NR, et al. Randomized clinical trial with two palliative radiotherapy regimens in painful bone metastases: 30 gy in 10 fractions compared with 8 gy in single fraction. Radiother Oncol. 2008;89(2):150\u20135.","journal-title":"Radiother Oncol"},{"issue":"1","key":"2419_CR13","first-page":"e2036","volume":"10","author":"M Shuja","year":"2018","unstructured":"Shuja M, Elghazaly AA, Iqbal A, Mohamed R, Marie A, Tunio MA, et al. Efficacy of 8 gy single fraction Palliative Radiation Therapy in painful bone metastases: a single Institution experience. Cureus. 2018;10(1):e2036.","journal-title":"Cureus"},{"issue":"2","key":"2419_CR14","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.ijrobp.2020.11.060","volume":"110","author":"BJ van der Pielkenrood","year":"2021","unstructured":"van der Pielkenrood BJ, Bartels MMT, Kasperts N, Verhoeff JJC, et al. Pain Response after Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in patients with bone Metastases-A phase 2 Randomized Controlled Trial within a prospective cohort. Int J Radiat Oncol Biol Phys. 2021;110(2):358\u201367.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"11","key":"2419_CR15","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1093\/jnci\/dji139","volume":"97","author":"W Hartsell","year":"2005","unstructured":"Hartsell W, Scott C, Bruner D, Scarantino C, Ivker R, Roach M, et al. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005;97(11):798\u2013804.","journal-title":"J Natl Cancer Inst"},{"issue":"7","key":"2419_CR16","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1001\/jamaoncol.2016.6770","volume":"3","author":"R McDonald","year":"2017","unstructured":"McDonald R, Ding K, Brundage M, Meyer R, Nabid A, Chabot P, et al. Effect of Radiotherapy on painful bone metastases: a secondary analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23. JAMA Oncol. 2017;3(7):953\u20139.","journal-title":"JAMA Oncol"},{"issue":"8","key":"2419_CR17","doi-asserted-by":"publisher","first-page":"4078","DOI":"10.1118\/1.3438081","volume":"37","author":"SH Benedict","year":"2010","unstructured":"Benedict SH, Yenice KM, Followill D, Galvin JM, Hinson W, Kavanagh B, et al. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010;37(8):4078\u2013101.","journal-title":"Med Phys"},{"key":"2419_CR18","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1016\/S1470-2045(15)00199-0","volume":"16","author":"E Chow","year":"2015","unstructured":"Chow E, Meyer R, Ding K, Nabid A, Chabot P, Wong P, et al. Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases:a double-blind, randomised placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16:1463\u201372.","journal-title":"Lancet Oncol"},{"key":"2419_CR19","doi-asserted-by":"publisher","unstructured":"Slotman D, Bartels M, Ferrer C, Bos C, Bartels L, Boomsma M et al. Focused Ultrasound and RadioTHERapy for non-invasive palliative pain treatment in patients with bone metastasis: a study protocol for the three-armed randomized controlled FURTHER trial. 2022; https:\/\/doi.org\/10.1186\/s13063-022-06942-1.","DOI":"10.1186\/s13063-022-06942-1"}],"container-title":["Radiation Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-024-02419-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13014-024-02419-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-024-02419-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T17:24:13Z","timestamp":1710264253000},"score":1,"resource":{"primary":{"URL":"https:\/\/ro-journal.biomedcentral.com\/articles\/10.1186\/s13014-024-02419-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,12]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2419"],"URL":"https:\/\/doi.org\/10.1186\/s13014-024-02419-4","relation":{},"ISSN":["1748-717X"],"issn-type":[{"value":"1748-717X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,12]]},"assertion":[{"value":"21 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study has been approved by the Cincinnati Children\u2019s Hospital Institutional Review Board. All subjects will provide informed consent prior to participating in study activities.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"N\/A.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Dr Mascia reported grants and personal fees from Varian Medical Systems during the conduct of the study. Dr Daugherty reported personal fees from Varian Medical Systems during the conduct of the study. Dr Sertorio reported grants from Varian Medical Systems during the conduct of the study. Ms Woo reported employment at Varian Medical Systems, the commercial sponsor of the study. Dr McCann reported employment at Varian Medical Systems, the commercial sponsor of the study. Dr Russell reported employment at Varian Medical Systems, the commercial sponsor of the study. Dr Sharma reported employment at Varian Medical Systems, the commercial sponsor of the study. Dr Khuntia reported employment at Varian Medical Systems, the commercial sponsor of the study, as well as multiple FLASH patents issued. Dr Bradley reported grants and personal fees from Varian Medical Systems outside the submitted work. Dr Simone reported personal fees from Varian Medical Systems during the conduct of the study. Dr Perentesis reported grants from Varian Medical Systems, Bristol Myers Squibb, Jazz Pharmaceuticals, and Incyte outside the submitted work. Dr Breneman reported funds from Varian Medical Systems to the institute during the conduct of the study and personal fees from Varian Medical Systems. No other disclosures were reported.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest disclosures"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34"}}