Open Access

Clara Grinzinger, Georg Stüben, Maria Neu, Anna Rubeck, Stefan Schiele, Lars Behrens, Klaus-Henning Kahl

• Purpose With increasing use of human epithelial growth factor receptor two (HER2)-targeted therapies, outcomes for numerous breast cancer patients have improved. Nevertheless, patients with HER2-positive tumours face a comparatively heightened risk for developing brain metastases (BM), which are often treated with stereotactic radiosurgery (SRS). Radionecrosis represents one of the clinically most significant adverse events of SRS. However, a knowledge gap remains regarding the effects of concurrent use of HER2-targeted therapies with SRS on development of radionecrosis, given conflicting findings in existing studies. Methods This systematic review was conducted in May 2024 through a search across electronic databases PubMed/MEDLINE and Cochrane library and was supplemented by citation searching and an artificial intelligence (AI) search. Results The literature search yielded 194 articles. After applying eligibility criteria, a total of 13 studies with 3219 patients totalPurpose With increasing use of human epithelial growth factor receptor two (HER2)-targeted therapies, outcomes for numerous breast cancer patients have improved. Nevertheless, patients with HER2-positive tumours face a comparatively heightened risk for developing brain metastases (BM), which are often treated with stereotactic radiosurgery (SRS). Radionecrosis represents one of the clinically most significant adverse events of SRS. However, a knowledge gap remains regarding the effects of concurrent use of HER2-targeted therapies with SRS on development of radionecrosis, given conflicting findings in existing studies. Methods This systematic review was conducted in May 2024 through a search across electronic databases PubMed/MEDLINE and Cochrane library and was supplemented by citation searching and an artificial intelligence (AI) search. Results The literature search yielded 194 articles. After applying eligibility criteria, a total of 13 studies with 3219 patients total were included, with approximately 270 patients in the topic-relevant subgroup. Investigated substances vary in different publications and include HER2 antibodies, antibody–drug conjugates (ADCs), such as trastuzumab emtansine (T-DM1), and kinase inhibitors. Four of six studies on ADCs demonstrated a higher risk for radionecrosis with concurrent administration. Two studies on lapatinib found no significant effects, as did as most studies investigating mainly HER2 antibodies. One publication reported an even lower risk for radionecrosis (RN) with concurrent use of HER2/EGFR tyrosine kinase inhibitors (TKIs). Conclusion While concurrent use of T‑DM1/ADCs seems associated to elevated radionecrosis risk, an ambiguous situation for other substances persists. Heterogenous study designs with varying substances, definitions of concurrent use, and radionecrosis parameters must be considered. Included studies are partly limited by sample size and retrospective study design. Therefore, clinical implications remain difficult to claim; further research on this topic is needed.…