LINACS: an ESTRO/OligoCare living systematic review of the safety of concurrent stereotactic radiotherapy and novel systemic therapies (version 1)
In brief
BRAF/MEK inhibitors and trastuzumab-emtansine raise severe radiation toxicity risk
A new living systematic review of 191 studies and 7,694 patients found markedly higher rates of grade 3 or greater radiation-related adverse events when stereotactic radiotherapy was combined with BRAF/MEK inhibitors or trastuzumab-emtansine. EGFR-targeted TKIs showed no excess toxicity, while anti-PD-(L)1 drugs had low radiation toxicity but more overall severe events after liver SRT. The continuously updated database (linacs.net) aims to keep clinicians informed as evidence rapidly expands.
- Journal
- Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Q1)
- Published
- 22 September 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Nora Sundahl, Esmée Lauren Looman, Luc Ollivier, Matteo Bagnalasta, Piet Ost, Matthias Guckenberger, et al.
- PMID
- 42772459
- DOI
- 10.1016/j.radonc.2026.111791
Why clinicians should know about it
- Picked for Radiation Oncology (paper of the day, 23 September 2026): Living systematic review of SRT + novel systemic therapies safety
Abstract
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 Conventional systematic reviews quickly become outdated, limiting their value for clinical decision-making.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).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.