TY  - JOUR
AU  - Daugherty, Emily C
AU  - Mascia, Anthony
AU  - Zhang, Yong
AU  - Lee, Eunsin
AU  - Xiao, Zhiyan
AU  - Sertorio, Mathieu
AU  - Woo, Jennifer
AU  - McCann, Claire
AU  - Russell, Kenneth
AU  - Levine, Lisa
AU  - Sharma, Ricky
AU  - Khuntia, Deepak
AU  - Bradley, Jeffrey
AU  - Simone II, Charles B
AU  - Perentesis, John
AU  - Breneman, John
PY  - 2023
DA  - 2023/1/5
TI  - FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases (FAST-01): Protocol for the First Prospective Feasibility Study
JO  - JMIR Res Protoc
SP  - e41812
VL  - 12
KW  - bone metastases
KW  - FLASH
KW  - proton therapy
KW  - external beam radiotherapy
KW  - palliative radiotherapy
KW  - extremities
KW  - pain relief
KW  - ultra-high dose rate
KW  - radiation therapy
KW  - cancer treatment
KW  - toxicity
KW  - oncology
KW  - radiotherapy
AB  - Background: In preclinical studies, FLASH therapy, in which radiation delivered at ultrahigh dose rates of ≥40 Gy per second, has been shown to cause less injury to normal tissues than radiotherapy delivered at conventional dose rates. This paper describes the protocol for the first-in-human clinical investigation of proton FLASH therapy. Objective: FAST-01 is a prospective, single-center trial designed to assess the workflow feasibility, toxicity, and efficacy of FLASH therapy for the treatment of painful bone metastases in the extremities. Methods: Following informed consent, 10 subjects aged ≥18 years with up to 3 painful bone metastases in the extremities (excluding the feet, hands, and wrists) will be enrolled. A treatment field selected from a predefined library of plans with fixed field sizes (from 7.5 cm × 7.5 cm up to 7.5 cm × 20 cm) will be used for treatment. Subjects will receive 8 Gy of radiation in a single fraction—a well-established palliative regimen evaluated in prior investigations using conventional dose rate photon radiotherapy. A FLASH-enabled Varian ProBeam proton therapy unit will be used to deliver treatment to the target volume at a dose rate of ≥40 Gy per second, using the plateau (transmission) portion of the proton beam. After treatment, subjects will be assessed for pain response as well as any adverse effects of FLASH radiation. The primary end points include assessing the workflow feasibility and toxicity of FLASH treatment. The secondary end point is pain response at the treated site(s), as measured by patient-reported pain scores, the use of pain medication, and any flare in bone pain after treatment. The results will be compared to those reported historically for conventional dose rate photon radiotherapy, using the same radiation dose and fractionation. Results: FAST-01 opened to enrollment on November 3, 2020. Initial results are expected to be published in 2022. Conclusions: The results of this investigation will contribute to further developing and optimizing the FLASH-enabled ProBeam proton therapy system workflow. The pain response and toxicity data acquired in our study will provide a greater understanding of FLASH treatment effects on tumor responses and normal tissue toxicities, and they will inform future FLASH trial designs. Trial Registration: : ClinicalTrials.gov NCT04592887; http://clinicaltrials.gov/ct2/show/NCT04592887 International Registered Report Identifier (IRRID): DERR1-10.2196/41812 
SN  - 1929-0748
UR  - https://www.researchprotocols.org/2023/1/e41812
UR  - https://doi.org/10.2196/41812
UR  - http://www.ncbi.nlm.nih.gov/pubmed/36206189
DO  - 10.2196/41812
ID  - info:doi/10.2196/41812
ER  -