• Ioannis I Verginadis, Deborah E Citrin, Bonnie Ky, Steven J Feigenberg, Alexandros G Georgakilas, Christine E Hill-Kayser, Constantinos Koumenis, Amit Maity, Jeffrey D Bradley, and Alexander Lin.
• Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: vioannis@pennmedicine.upenn.edu.
• Lancet. 2025 Jan 25; 405 (10475): 338352338-352.

AbstractFor 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.Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

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