000304998 001__ 304998 000304998 005__ 20251005022951.0 000304998 0247_ $$2doi$$a10.1016/j.annonc.2025.09.008 000304998 0247_ $$2pmid$$apmid:41016600 000304998 0247_ $$2ISSN$$a0923-7534 000304998 0247_ $$2ISSN$$a1569-8041 000304998 0247_ $$2altmetric$$aaltmetric:181744969 000304998 037__ $$aDKFZ-2025-01989 000304998 041__ $$aEnglish 000304998 082__ $$a610 000304998 1001_ $$avan Aken, E. S. M.$$b0 000304998 245__ $$aESMO-ESTRO consensus statements on the safety of combining radiotherapy with immune checkpoint inhibitors, VEGF(R) inhibitors, or multitargeted tyrosine kinase inhibitors. 000304998 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2025 000304998 3367_ $$2DRIVER$$aarticle 000304998 3367_ $$2DataCite$$aOutput Types/Journal article 000304998 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1759230392_31253 000304998 3367_ $$2BibTeX$$aARTICLE 000304998 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000304998 3367_ $$00$$2EndNote$$aJournal Article 000304998 500__ $$aepub 000304998 520__ $$aThe combination of radiotherapy (RT) with targeted agents or immunotherapy may result in improved outcomes, but it can also increase toxicity. However, there is a paucity of high-quality toxicity data, leading to an absence of evidence-based guidelines.To address this, ESMO and ESTRO initiated a series of systematic reviews followed by a Delphi consensus process to develop multidisciplinary, evidence-based consensus statements regarding the safety of combining RT with such agents. The current publication describes the combination of RT with immune checkpoint inhibitors (ICIs), vascular endothelial growth factor (receptor) (VEGF(R)) inhibitors, or multitargeted tyrosine kinase inhibitors (TKIs). By systematically covering different drug classes and irradiated areas, 76 clinical scenarios were evaluated during two Delphi rounds with 20 international experts. Safety statements were developed for each scenario, based on the systematic literature reviews.A total of 5,921 records were screened during the systematic literature review process for ICIs, VEGF(R) inhibitors and multitargeted TKIs, and 159 reports were selected for inclusion in the final literature reviews and the database. During the two Delphi rounds, agreement was reached regarding the safety statements for 74 clinical scenarios.Generally, the expected toxicity of combining RT with ICIs is low, particularly for PD-(L)1 inhibitors. For most combinations with VEGF(R) inhibitors and multitargeted TKIs, exercising caution is recommended. The evidence-based safety statements developed during this comprehensive project, provide practical guidance on combining RT with targeted cancer therapies and immunotherapy. 000304998 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x0 000304998 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000304998 650_7 $$2Other$$aConsensus statements 000304998 650_7 $$2Other$$aImmune checkpoint inhibitors 000304998 650_7 $$2Other$$aRadiotherapy 000304998 650_7 $$2Other$$aSystematic review 000304998 650_7 $$2Other$$aToxicity 000304998 650_7 $$2Other$$aTyrosine kinase inhibitors 000304998 7001_ $$aDevnani, B.$$b1 000304998 7001_ $$aPrelaj, A.$$b2 000304998 7001_ $$aCastelo-Branco, L.$$b3 000304998 7001_ $$aMarijnen, C. A. M.$$b4 000304998 7001_ $$aMartins-Branco, D.$$b5 000304998 7001_ $$aGambacorta, M. A.$$b6 000304998 7001_ $$aLamarca, A.$$b7 000304998 7001_ $$aHarrington, K.$$b8 000304998 7001_ $$aMinniti, G.$$b9 000304998 7001_ $$aHecht, M.$$b10 000304998 7001_ $$aPapamichael, D.$$b11 000304998 7001_ $$0P:(DE-He78)4be9ccb23f3e472b97743845cd2b3fe9$$aKrause, M.$$b12$$udkfz 000304998 7001_ $$aCathomas, R.$$b13 000304998 7001_ $$aLindberg, K.$$b14 000304998 7001_ $$aO'Cathail, S. M.$$b15 000304998 7001_ $$aNestle, U.$$b16 000304998 7001_ $$aBarriuso, J.$$b17 000304998 7001_ $$aNowicki, S.$$b18 000304998 7001_ $$0P:(DE-HGF)0$$aRödel, C.$$b19 000304998 7001_ $$aBoot, P.$$b20 000304998 7001_ $$aBelka, C.$$b21 000304998 7001_ $$aRicardi, U.$$b22 000304998 7001_ $$aLordick, F.$$b23 000304998 7001_ $$aDe Ruysscher, D.$$b24 000304998 7001_ $$aPentheroudakis, G.$$b25 000304998 7001_ $$ade Jong, M. C.$$b26 000304998 7001_ $$aGandhi, A. K.$$b27 000304998 773__ $$0PERI:(DE-600)2003498-2$$a10.1016/j.annonc.2025.09.008$$gp. 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