KEY POINTS
- The first LINACS living systematic review included 191 studies and 7,694 patients receiving intracranial or extracranial stereotactic RT within 30 days of a novel systemic therapy. Of these studies, 97 were prospective and 94 retrospective, and the review is designed for biannual updating.
- The evidence base has expanded rapidly: compared with the previous 2023 systematic review, LINACS included nearly three times as many patients and identified data for 14 additional drug groups or combinations. Importantly, the authors treat pooled toxicity rates as descriptive synthesis rather than a formal meta-analysis.
- Multi-target TKIs appeared relatively reassuring overall: among 770 patients, grade ≥3 overall treatment-related events occurred in 16.5% and RT-related events in 1.8%. However, liver SRT with lenvatinib or sorafenib was different: 56/138 patients (40.5%) developed grade ≥3 overall adverse events.
- EGFR-targeting TKIs showed no clear excess signal with lung SRT. Across 500 patients, grade ≥3 overall adverse events occurred in approximately 15.6–17.5%, with RT-related grade ≥3 events in 6.4% of 203 evaluable patients.
- BRAF/MEK inhibition generated one of the clearest caution signals. Among 44 patients, grade ≥3 RT-related toxicity occurred in 20.5%; among 38 receiving brain SRT, 8 patients (21%) experienced high-grade RT-related events.
- Antibody-drug conjugates were heterogeneous. Across 105 patients, grade ≥3 RT-related events occurred in 10.5%, but among 19 patients receiving brain SRT near trastuzumab emtansine, 6 (31.6%) experienced high-grade RT-related toxicity; no comparable excess signal was identified for trastuzumab deruxtecan or sacituzumab govitecan.
- Anti-PD-(L)1 therapy had relatively low RT-related toxicity overall: 6.4% in 582 evaluable patients, with no clear excess signal for brain, lung, pancreas or bone SRT. Liver SRT again stood out, with grade ≥3 overall events in 30.3% of 175 patients, although laboratory abnormalities and concurrent transarterial embolization complicated attribution.
CLINICAL TAKEAWAY
SRT can often be delivered near modern systemic therapy without an obvious excess of severe toxicity, but safety is highly drug- and site-specific. BRAF/MEK inhibitors, trastuzumab emtansine with brain SRT, and liver SRT with selected agents deserve particular caution; inconsistent reporting of drug interruption means this review cannot define optimal hold intervals.