A phase I dose escalation of FLASH radiotherapy in patients with cutaneous metastases from melanoma: The IMPulse trial
Abstract
Introduction: The observation in preclinical studies that FLASH radiotherapy (FLASH-RT) can spare normal tissues while maintaining its anti-tumoral effect provided the rational for its clinical translation. In this context, this clinical trial presents the first-in-human dose-escalation trial of FLASH-RT.
Materials and methods: This phase I clinical trial enrolled patients presenting progressive melanoma with cutaneous metastases refractory to systemic treatment. A 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD), starting at 22 Gy and escalating in 2 Gy increments up to 28 Gy. Dose-limiting toxicity (DLT) was defined as any Grade ≥ 3 adverse event occurring in the irradiated field within 4 weeks post-RT. FLASH-RT was delivered using a 9 MeV Mobetron (IntraOp, USA) at a dose rate exceeding 200 Gy/s, delivered in 10 pulses over 90 ms. For all patients, dosimetry was performed using alanine, thermoluminescent dosimeters (TLD), and films.
Results: Between June 2021 and September 2024, 11 patients were enrolled, with 15 lesions treated in 10 out of these patients. One patient was enrolled at two different dose levels for distinct lesions. The trial initially aimed to dose escalation up to 34 Gy but was discontinued after completing of dose level 28 Gy due to slow accrual. No DLTs were observed at any of the administered dose levels (22-28 Gy), and the MTD was not reached.
Conclusion: Dose escalation of FLASH-RT delivered in a single fraction up…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
Read the paper
Related studies
- Preliminary Toxicity Analysis of 3DCRT versus IMRT on the High Dose Arm of the RTOG 0126 Prostate Cancer Trial
- Adaptive Radiotherapy for Head and Neck Cancer: Initial Clinical Outcomes from a Prospective Trial
- American Association of Physicists in Medicine Task Group 263: Standardizing Nomenclatures in Radiation Oncology
- Motion Management Strategies and Technical Issues Associated with Stereotactic Body Radiotherapy of Thoracic and Upper Abdominal Tumors: A Review from NRG Oncology
- High-dose-rate interstitial brachytherapy as a monotherapy for localized prostate cancer: treatment description and preliminary results of a phase I/II clinical trial
- Highly efficient training, refinement, and validation of a knowledge-based plan quality control system for radiotherapy clinical trials
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.