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ESMO-ESTRO consensus statements on the safety of combining radiotherapy with CDK4/6, HER2, PARP, or mTOR inhibitors.

Evert S M van Aken ,
Ajeet Kumar Gandhi ,
Sean M O'Cathail ,
Gerben Borst ,
Jorge Barriuso ,
Emmanouil Fokas ,
Luis Castelo-Branco ,
Anne Hansen Ree ,
Evandro de Azambuja ,
Stephanie Kroeze ,
Ilaria Colombo ,
Antonin Levy ,
Carmen Criscitiello ,
Maximilian Niyazi ,
Nadia Harbeck ,
Ewa Szutowicz ,
Gabor Liposits ,
Marcel Verheij ,
Isabelle Ray-Coquard ,
Paolo Tarantino ,
Dario Trapani ,
Paulien Boot ,
Claus Belka ,
Dirk De Ruysscher ,
George Pentheroudakis ,
Corrie A M Marijnen ,
Florian Lordick ,
Umberto Ricardi ,
Diogo Martins-Branco ,
Arsela Prelaj ,
Monique C de Jong ,
Bharti Devnani

Abstract

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.

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.

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.

More about this publication

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

Volume 215
Pages 111330
Publication date 01-02-2026

Full text links

Publisher website (DOI) 10.1016/j.radonc.2025.111330
Europe PubMed Central 41389857
Pubmed 41389857

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