LINACS: an ESTRO/OligoCare living systematic review of the safety of concurrent stereotactic radiotherapy and novel systemic therapies (version 1).

BACKGROUND: New safety evidence on the combination of stereotactic radiotherapy (SRT) and novel systemic therapies is emerging at an accelerating pace. Conventional systematic reviews quickly become outdated, limiting their value for clinical decision-making. AIM: We established the first living systematic review on this topic, providing continuously updated evidence through biannual literature surveillance and immediate online dissemination (https://linacs.net). This dynamic approach delivers current estimates of high-grade adverse events (AEs) to support evidence-based practice. METHODS: Search terms (including newly approved drugs), searches and analyses are updated biannually. PubMed is searched (from January 1, 2000) for studies reporting original data on patients receiving SRT within 30 days of novel systemic therapy. Current search: April 2, 2026. Studies with a high risk of bias are excluded as per standard methods. The primary outcomes are pooled estimates of grade ≥ 3 overall treatment-related AEs (OAE) and RT-related AEs (RTAE). PROSPERO registration: CRD42024559453. RESULTS: 191 studies comprising 7,694 patients were included-nearly tripling the evidence base of the last published conventional systematic review in 2023 and covering 14 additional drug groups (combinations). EGFR-targeting TKIs showed no clear evidence of excess AEs. Substantial RTAE rates were observed for BRAF/MEK inhibitors and trastuzumab-emtansine. Although anti-PD-(L)1 therapies and multi-target TKIs had low overall RTAE rates, both were associated with high OAEs following liver SRT. CONCLUSIONS: Given the exponential growth of evidence, this living systematic review offers a new model for delivering current clinical guidance by collecting and reanalyzing all available data biannually and making it immediately accessible online (https://linacs.net).