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Review
. 2025 Jul:208:110910.
doi: 10.1016/j.radonc.2025.110910. Epub 2025 Apr 30.

ESMO-ESTRO framework for assessing the interactions and safety of combining radiotherapy with targeted cancer therapies or immunotherapy

Evert S M van Aken  1 , Bharti Devnani  2 , Luis Castelo-Branco  3 , Dirk De Ruysscher  4 , Diogo Martins-Branco  5 , Corrie A M Marijnen  6 , Barbara Muoio  7 , Claus Belka  8 , Florian Lordick  9 , Stephanie Kroeze  10 , George Pentheroudakis  5 , Dario Trapani  11 , Umberto Ricardi  12 , Ajeet Kumar Gandhi  13 , Arsela Prelaj  14 , Sean M O'Cathail  15 , Monique C de Jong  16
Affiliations
Free article
Review

ESMO-ESTRO framework for assessing the interactions and safety of combining radiotherapy with targeted cancer therapies or immunotherapy

Evert S M van Aken et al. Radiother Oncol. 2025 Jul.
Free article

Abstract

With the emergence of targeted therapies and immunotherapy, various cellular pathways are utilized to improve tumor control and patient survival. In patients receiving these new agents, radiotherapy is commonly applied with both radical and palliative intent. Combining radiotherapy with targeted therapies or immunotherapy may improve treatment outcomes, but may also lead to increased toxicity. High-quality toxicity data and evidence-based guidelines regarding combined therapy are very limited. The present framework, developed by ESMO and ESTRO, explores the main biological effects and interaction mechanisms of radiotherapy combined with targeted agents or immunotherapy. It addresses general clinical factors to take into consideration when deciding on whether and/or how to combine radiotherapy with these agents. Furthermore, it provides pragmatic, biological mechanism-based, clinical considerations for combining radiotherapy with various targeted agents or immunotherapy.

Keywords: Combined modality therapy; Immune checkpoint blockade; Interaction; Radiobiology; Radiotherapy; Toxicity; Tyrosine kinase inhibitors.

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Conflict of interest statement

Declaration of competing interest Bharti Devnani has declared non-financial interests as a member of ASTRO, Indian Society of Neuro-Oncology, Indian Society of Oncology, Association of Radiation Oncologists; Leadership role for Oncoalert. Luis Castelo-Branco has declared speaker engagements from AiCME, Eversana, and Novacure; employment from ESMO (2021-2023); Advisory role with the World Health Organization. Dirk De Ruysscher has declared institutional financial interests (no personal financial interests) for AstraZeneca, BMS, Beigene, Philips, Olink, Eli-Lilly. Diogo Martins-Branco has declared full-time employment from the European Society for Medical Oncology since September 1, 2023; participation as medical research fellow in research studies institutionally funded by Eli Lilly, F. Hoffmann-La Roche Ltd, and Novartis to Institut Jules Bordet (2021-2023); and non-financial interests as a board member of Associação de Investigação e Cuidados de Suporte em Oncologia (2022-2024) and member of American Society of Clinical Oncology, Associação Portuguesa de Cuidados Paliativos, Multinational Association of Supportive Care in Cancer, and Sociedade Portuguesa de Oncologia. Barbara Muoio has declared advisory board role for Immedica Pharma, Pharmamar, Servier; and Invitation to ESMO 2024 congress from Roche. Florian Lordick has declared speaker engagement for Art Tempi, Astellas, AstraZeneca, BMS, Daiichi Sankyo, Eli Lilly, Imedex, Incyte, Medscape, MedUpdate, Merck Serono, MSD, Servier, and StreamedUp!; advisory board role for Astellas, Beigene, BMS, Daiichi Sankyo, MSD and PAGE; institutional research grants from AstraZeneca, BMS, and Gilead; Writing engagement for Deutscher Arzteverlag, Elsevier, Iomedico; Expert Testimony for Biontech; Institutional interest as Coordination PI for Beigene and Daiichi Sankyo. George Pentheroudakis has declared full-time employment as Chief Medical Officer at ESMO; non-financial interests as a member of ASCO, Hellenic Cooperative Oncology Group (HeCOG), and Hellenic Society of Medical Oncology. Dario Trapani has declared non-financial interests as a member of the EMA Healthcare Professional Working Party and WHO’s Cancer Medicines Working Group (CMWG, SAGE IVD). Umberto Ricardi has declared advisory board role and speaker engagement for AstraZeneca; institutional support from BrainLab. Arsela Prelaj has declared speaker’s engagement from Lilly, MEDSIR, Novartis, and Roche; advisory board role for AstraZeneca, BMS, Janssen; institutional funding as local PI for BAYER, BMS, Lilly, MSD, Roche: Institutional funding as coordinating PI for AstraZeneca and Spectrum; travel grant from Janssen; funding for Training of personnel from AstraZeneca and Italfarma. Sean M. O’Cathail has declared advisory board role for Artios Pharmaceuticals; speaker engagement for Servier; and institutional research grant from Varian Medical Systems. All other authors have declared no conflict of interest.

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