Incidence of adverse events of concomitant immune checkpoint inhibitors and ultra hypo-fractionated radiotherapy: systematic review and meta-analysis
In brief
Severe colitis affected 1.1% receiving immunotherapy with ultra-short radiation
Across 2,057 patients in 53 trials, severe colitis occurred in 1.1%, severe pneumonitis in 0.5%, and severe skin rash in 0.2% after combined immune checkpoint inhibitors and ultra-short-course radiation. Researchers found no consistent signal of more systemic toxicity than previously reported with immunotherapy alone, but this comparison was not a direct test against a control group.
- Journal
- Clinical and translational radiation oncology (Q1)
- Published
- 24 October 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Nicklas Juel Spindler, Rikke Løvendahl Eefsen, Gitte Fredberg Persson, Dorte Lisbet Nielsen, Carsten Bogh Juhl
- PMID
- 42990844
- DOI
- 10.1016/j.ctro.2026.101328
Why clinicians should know about it
- Picked for Radiation Oncology (paper of the day, 8 November 2026): Quantifies toxicity of concurrent immune checkpoint inhibitors and ultra-hypofractionated RT
Abstract
BACKGROUND: The combination of ultra hypofractionated radiotherapy (U-HFRT) and immune checkpoint inhibitors (ICIs) has been proposed to increase systemic anti-tumor response, but the incidence of toxicity after concomitant ICI and U-HFRT remains to be explored. METHODS: We performed a systematic review and meta-analysis of the incidence of adverse events (AEs) after concomitant ICI and U-HFRT in prospective trials, to evaluate whether ICI and U-HFRT were more toxic than ICI monotherapy. Eligible studies reported ≥10 adults treated with concomitant ICI and U-HFRT given to boost the immune response, here defined as ≥5 Gray per fraction and ≤ 10 fractions in total. The primary outcome was the incidence of selected National Cancer Institute Common Toxicity Criteria of Adverse Events (CTCAE) of any grade and grade 3-4 (G3-4). Secondary outcomes were median overall survival (mOS) and median progression-free survival (mPFS). The incidence of the AEs was calculated by a random-effects meta-analysis model and stratified by ICI drug groups, single vs. multiple fractions, and mean biological effective dose ≥44 Gy vs. < 44 Gy (mean BED). Quality assessment was performed with the McMaster Quality Assessment Scale for Harms (McHarm). RESULTS: The meta-analysis included 2057 patients from 52 phase I-II and one phase III study. Overall, the most frequent G3-4 AEs were colitis (1.1%), pneumonitis (0.5%), and skin rash (0.2%). The incidence of any-grade pneumonitis was 3.3% in patients treated with anti-PD-1/PD-L1 and U-HFRT. The mOS and mPFS were 10.2 and 3.9 months across all cancer types, respectively. CONCLUSION: There was no consistent signal of increased incidence of systemic toxicity after concomitant U-HFRT and ICI in the phase I-III trials compared to previously reported toxicities of ICI monotherapy.
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.