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The Ewha Medical Journal
Ewha Womans University School of Medicine

Ewha Med J 47(4)

pISSN: 2234-3180, eISSN: 2234-2591

DOI: https://doi.org/10.12771/emj.2024.e54

Review

FLASH radiotherapy: bridging revolutionary mechanisms and clinical frontiers in cancer treatment – a narrative review

Jae Sik Kim1, Hak Jae Kim2,3,*
1Department of Radiation Oncology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Korea.
2Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, , Seoul 03080, Korea.
3Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
*Corresponding Author: Hak Jae Kim, Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, , Seoul 03080, Korea, Republic of. Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea, Republic of. E-mail: khjae@snu.ac.kr.

© Copyright 2024 Ewha Womans University School of Medicine. This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: Aug 21, 2024; Accepted: Sep 23, 2024

Published Online: Oct 31, 2024

Abstract

FLASH radiotherapy (FLASH-RT) is an innovative approach that delivers ultra-high dose rates (UHDR) exceeding 40 Gy in less than a second, aiming to widen the therapeutic window by minimizing damage to normal tissue while maintaining tumor control. This review explores the advancements, mechanisms, and clinical applications of FLASH-RT across various radiation sources. Electrons have been predominantly used due to technical feasibility, but their limited penetration depth restricts clinical application. Protons, offering deeper tissue penetration, are considered promising for treating deep-seated tumors despite challenges in beam delivery. Preclinical studies demonstrate that FLASH-RT reduces normal tissue toxicity in the lung, brain, skin, intestine, and heart without compromising antitumor efficacy. The mechanisms underlying the FLASH effect may involve oxygen depletion leading to transient hypoxia, reduced DNA damage in normal tissues, and modulation of immune and inflammatory responses. However, these mechanisms are incompletely understood, and inconsistent results across studies highlight the need for further research. Initial clinical studies, including treatment of cutaneous lymphoma and bone metastases, indicate the feasibility and potential benefits of FLASH-RT in patients. Challenges for clinical implementation include technical issues in dosimetry accuracy at UHDR, adaptations in treatment planning systems, beam delivery methods, and economic considerations due to specialized equipment requirements. Future directions will involve comprehensive preclinical studies to optimize irradiation parameters, large-scale clinical trials to establish standardized protocols, and technological advancements to overcome limitations. FLASH-RT holds the potential to revolutionize radiotherapy by reducing normal tissue toxicity and improving therapeutic outcomes, but significant research is required for real-world clinical applications.

Keywords: DNA damage; Electrons; Hypoxia; Neoplasms; Protons