TY - JOUR
T1 - ESMO-ESTRO consensus statements on the safety of combining radiotherapy with CDK4/6, HER2, PARP, or mTOR inhibitors
AU - van Aken, Evert S.M.
AU - Gandhi, Ajeet Kumar
AU - O'Cathail, Sean M.
AU - Borst, Gerben
AU - Barriuso, Jorge
AU - Fokas, Emmanouil
AU - Castelo-Branco, Luis
AU - Ree, Anne Hansen
AU - de Azambuja, Evandro
AU - Kroeze, Stephanie
AU - Colombo, Ilaria
AU - Levy, Antonin
AU - Criscitiello, Carmen
AU - Niyazi, Maximilian
AU - Harbeck, Nadia
AU - Szutowicz, Ewa
AU - Liposits, Gabor
AU - Verheij, Marcel
AU - Ray-Coquard, Isabelle
AU - Tarantino, Paolo
AU - Trapani, Dario
AU - Boot, Paulien
AU - Belka, Claus
AU - Ruysscher, Dirk De
AU - Pentheroudakis, George
AU - Marijnen, Corrie A.M.
AU - Lordick, Florian
AU - Ricardi, Umberto
AU - Martins-Branco, Diogo
AU - Prelaj, Arsela
AU - de Jong, Monique C.
AU - Devnani, Bharti
N1 - Funding Information:
The panel would like to acknowledge the contributions of Klizia Ambra Marinoni and Fiona Perdomo from the Scientific and Medical Affairs Department at ESMO for their expert consultation on the Delphi methodology and the shared project coordination, and of Eralda Azizaj for providing logistical and administrative support from ESTRO. Furthermore, the panel wishes to thank the external reviewers, Icro Meattini and Orit Kaidar-Person, for their valuable comments and advice, which contributed to improving the quality of the manuscript.
Publisher Copyright:
© 2025 The Author(s)
PY - 2026/2/1
Y1 - 2026/2/1
N2 - Background: While combining radiotherapy (RT) with targeted agents or immunotherapy may improve outcomes, it may also increase toxicity. High-quality toxicity data and multidisciplinary, evidence-based guidelines on the combination of these treatment modalities are scarce. Design: The European Society for Medical Oncology (ESMO) and the European SocieTy for Radiotherapy and Oncology (ESTRO) developed a series of systematic reviews with multidisciplinary, tumor-agnostic, evidence-based Delphi consensus statements regarding the safety of combining RT with targeted agents or immunotherapy. The current study addresses the safety of combining RT with CDK4/6 inhibitors, anti-HER2 monoclonal antibodies, PARP inhibitors, or mTOR-inhibitors. During the modified Delphi process, two digital voting rounds were organized with 18 international experts. By systematically evaluating the different drug classes and irradiated areas, 74 clinical scenarios were assessed. Safety statements were formulated for all scenarios, based on the evidence from the systematic literature reviews. Results: A total of 1,341 records were screened during the systematic literature reviews, of which 107 studies were ultimately included in the final reviews and the literature database. After two Delphi voting rounds, agreement was reached on all 74 scenario-specific safety statements. Conclusions: The expected combined toxicity is often low for anti-HER2 monoclonal antibodies. For most scenarios with CDK4/6, PARP, or mTOR inhibitors, exercising caution is recommended.
AB - Background: While combining radiotherapy (RT) with targeted agents or immunotherapy may improve outcomes, it may also increase toxicity. High-quality toxicity data and multidisciplinary, evidence-based guidelines on the combination of these treatment modalities are scarce. Design: The European Society for Medical Oncology (ESMO) and the European SocieTy for Radiotherapy and Oncology (ESTRO) developed a series of systematic reviews with multidisciplinary, tumor-agnostic, evidence-based Delphi consensus statements regarding the safety of combining RT with targeted agents or immunotherapy. The current study addresses the safety of combining RT with CDK4/6 inhibitors, anti-HER2 monoclonal antibodies, PARP inhibitors, or mTOR-inhibitors. During the modified Delphi process, two digital voting rounds were organized with 18 international experts. By systematically evaluating the different drug classes and irradiated areas, 74 clinical scenarios were assessed. Safety statements were formulated for all scenarios, based on the evidence from the systematic literature reviews. Results: A total of 1,341 records were screened during the systematic literature reviews, of which 107 studies were ultimately included in the final reviews and the literature database. After two Delphi voting rounds, agreement was reached on all 74 scenario-specific safety statements. Conclusions: The expected combined toxicity is often low for anti-HER2 monoclonal antibodies. For most scenarios with CDK4/6, PARP, or mTOR inhibitors, exercising caution is recommended.
KW - Consensus statements
KW - Radiotherapy
KW - Systematic review
KW - Targeted therapy
KW - Toxicity
U2 - 10.1016/j.radonc.2025.111330
DO - 10.1016/j.radonc.2025.111330
M3 - Article
SN - 0167-8140
VL - 215
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
M1 - 111330
ER -