ESTRO 2025 - Abstract Book

S1669

Clinical - Sarcoma & skin cancer & malignant melanoma

ESTRO 2025

Purpose/Objective: In pre-clinical studies, FLASH radiotherapy (RT), delivering irradiation in milliseconds, compared to minutes for conventional RT, induces a remarkable sparing of normal healthy tissues, while the efficacy on tumors is preserved intact. Clinical data are currently missing and this study is the first dose escalation trial of FLASH radiotherapy. Material/Methods: This is a phase I, first-in-human, dose-escalation trial to assess electron FLASH-RT in patients with progressive skin metastases of melanoma resistant to systemic treatments. Following a classical 3+3 design, this trial aimed to establish the maximum tolerated dose (MTD) with escalation in 2 Gy increments, starting at 22 Gy potentially up to 34 Gy in the absence of dose-limiting toxicity (DLT). Definition of DLT included Grade ≥ 3 adverse event (CTCAE v5) skin reactions occurring inside the irradiated field within 4 weeks post-treatment (photographs were analyzed centrally by a panel of experts). FLASH dose was delivered at 10 MeV Mobetron (IntraOp, USA) with a dose rate higher than 200Gy/s, administered in 10 pulses in 90ms. For all patients dosimetry was performed using alanine, TLD and films. Results: Eight patients were treated between 2021 and 2024, with two patients treated twice at two different dose levels. The median age was 77.5 years (range 64-94), and Karnofsky Performance Status (KPS) scores ranged from 70 to 100%. A total of 14 lesions were irradiated. The mean tumor size was 14.5mm (+/- 6.7 SD). Median follow-up was 3.8 months (range 0.2-12.6). All patients completed the DLT surveillance period, however one of the patients enrolled twice did not complete the DLT surveillance period after the second enrollment. Four dose level were completed at 22 Gy, 24 Gy, 26 Gy and 28 Gy without DLT. Six patients experienced G1 radiation-induced epithelitis. The highest acute adverse event toxicity observed was Grade 2 in one patient at 24 Gy. After treatment, the mean tumor size reduction was 41%. The dosimetry confirmed a delivered dose within 4% compared to the prescribed dose in all cases. Conclusion: The first 4 doses levels were successfully completed. A single fraction of FLASH-RT administered to skin metastases of melanoma did not result in DLT up to 28 Gy. There was no increase of acute skin reactions, while increasing the dose.

Keywords: FLASH radiotherapy - Melanoma - Phase 1

1222

Poster Discussion Results of Neoadjuvant Radiotherapy in High-Grade Soft Tissue Sarcomas of the Extremities: Insights from an Italian Reference Centre Silvia Cammelli 1,2 , Viola Laghi 1 , Paolo Spinnato 3 , Erika Galietta 1,2 , Costanza M Donati 1,2 , Letizia Cavallini 1,2 , Arina A Zamfir 1 , Giuseppe Bianchi 4 , Alberto Righi 5 , Massimiliano De Paolis 6 , Andrea Sambri 6 , Annalisa Cortesi 7 , Claudio Malizia 8 , Davide M Donati 4 , Alessio G Morganti 1,2 1 Radiation Oncolgy, IRCCS Azienda Ospedaliero-Universitaria di Bologna,, Bologna, Italy. 2 Department of Medical and Surgical Sciences (DIMEC),, Alma Mater Studiorum University of Bologna, Bologna, Italy. 3 Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 4 Orthopedic musculo-skeletal oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 5 Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 6 Orthopedic and Traumatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna,, Bologna, Italy. 7 Radiotherapy Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori",, Forlì-Cesena, Italy. 8 Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna,, Bologna, Italy