FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases (FAST-01): Protocol for the First Prospective Feasibility Study

Abstract

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; https://ichgcp.net/clinical-trials-registry/NCT04592887.

International registered report identifier (irrid): DERR1-10.2196/41812.

Keywords: FLASH; bone metastases; cancer treatment; external beam radiotherapy; extremities; oncology; pain relief; palliative radiotherapy; proton therapy; radiation therapy; radiotherapy; toxicity; ultra-high dose rate.

Conflict of interest statement

Conflicts of Interest: ECD has received small honoraria from Varian Speakers Bureau for a February 2022 virtual talk. ZX is a principal investigator of a preclinical research grant from Varian, a Siemens Healthineers company. The grant goes to the author’s institution. MS is a private investigator on a pre-clinical research grant from Varian, a Siemens Healthineers company; the grant goes to the author's institution. JW, CMC, KR, LL, RS and DK are employees of Varian, and CBS is a Varian Medical Systems consultant. JP is the principal investigator of a multi-investigator research program contract between his institution and Varian Medical Systems; the funding goes to the author's institution. JP's institution also receives funding for the execution of FLASH clinical trials. JP does not receive honoraria or other forms of payment from Varian Medical Systems, and the author follows their institutional policy toward conflicts of interest in this consultant role. JB is a principal investigator of a research grant from Varian Medical Systems; the grant funding goes to the author’s institution. JB is also a consultant for Varian, involved in its application to the Food and Drug Administration for FLASH radiotherapy. The author follows the policy of his institute in terms of the conflicts of interest in this consultant role. The remaining authors have no conflicts of interest to declare.

©Emily C Daugherty, Anthony Mascia, Yong Zhang, Eunsin Lee, Zhiyan Xiao, Mathieu Sertorio, Jennifer Woo, Claire McCann, Kenneth Russell, Lisa Levine, Ricky Sharma, Deepak Khuntia, Jeffrey Bradley, Charles B Simone II, John Perentesis, John Breneman. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.01.2023.