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Review
. 2025 Jan 25;405(10475):338-352.
doi: 10.1016/S0140-6736(24)02319-5. Epub 2025 Jan 16.

Radiotherapy toxicities: mechanisms, management, and future directions

Affiliations
Review

Radiotherapy toxicities: mechanisms, management, and future directions

Ioannis I Verginadis et al. Lancet. .

Abstract

For over a century, radiotherapy has revolutionised cancer treatment. Technological advancements aim to deliver high doses to tumours with increased precision while minimising off-target effects to organs at risk. Despite advancements such as image-guided, high-precision radiotherapy delivery, long-term toxic effects on healthy tissues remain a great clinical challenge. In this Review, we summarise common mechanisms driving acute and long-term side-effects and discuss monitoring strategies for radiotherapy survivors. We explore ways to mitigate toxic effects through novel technologies and proper patient selection and counselling. Additionally, we address policies and management strategies to minimise the severity and impact of toxicity during and after treatment. Finally, we examine the potential advantages of emerging technologies and innovative approaches to improve conformity, accuracy, and minimise off-target effects.

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Conflict of interest statement

Declaration of interests This work received no dedicated funding. IIV reports research funding from the Institute for Translational Medicine and Therapeutics, American Cancer Society, the Thomas B and Jeannette E Laws McCabe Fund, and the University Research Foundation, paid to institution; honoraria from the University of Arkansas (Fayetteville, AR, USA); consulting fees from Mevion Medical Systems; and travel support from the Flash Radiotherapy & Particle Therapy (FRPT) and Radiation Research Society (RRS) to attend the FRPT and RRS meetings. DEC is an employee at the US National Institutes of Health; and is a non-fiduciary, unpaid, nominating committee member of the American Society of Radiation Oncology. BK reports research funding from the US National Institutes of Health, the American Heart Association, and the Pfizer Investigator Initiated Grant, paid to institution; consulting fees from Bristol Myers Squibb, AstraZeneca, Roche, and Pfizer; honoraria from Medscape, UpToDate, and the American College of Cardiology Cardio-Oncology CME Course; support to attend the American Society of Clinical Oncology and American Association for Cancer Research meetings; is Editor-in-Chief of JACC CardioOncology; and is part of the Board of Trustees of the American College of Cardiology. CK reports research funding from the US National Institutes of Health, The Mark Foundation for Cancer Research, and Ion Beam Applications group through a sponsored research agreement to his institution; honoraria from MD Anderson Cancer Center, Dartmouth University (Hanover, NH, USA), and Duke University (Durham, NC, USA); support from the American Association for Cancer Research to attend the American Association for Cancer Research meeting; and is a Scientific Founder and majority stock option holder of Veltion Therapeutics. AM reports honoraria from the Oncology Nursing Society and University of Washington (Washington, DC, USA). JDB reports honoraria from Mevion Medical Systems. AL reports research funding from the US National Institutes of Health and the Patient-Centered Outcomes Research Institute, honoraria from Galera Therapeutics for participating in their advisory board, and honoraria from Janssen Pharmaceuticals for participation in their steering committee. All other authors declare no competing interests.

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