Incidence of Radiation Pneumonitis Following EGFR-TKI Combined With Thoracic Radiotherapy in Unresectable Stage III...

To evaluate the incidence of radiation pneumonitis (RP) in unresectable stage III/IV non-small-cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT).

We systematically searched databases through December 2025. Studies reporting RP incidence (CTCAE/RTOG criteria) in NSCLC patients receiving any-generation EGFR-TKI with TRT were included. Pooled incidence rates (95% confidence interval [CI]) were calculated using a random-effects model.

Twenty studies involving 693 patients were included. The pooled overall incidence of RP was 62.06% (95% CI, 48.67-74.63). Grade 1-2 RP occurred in 52.09% (95% CI, 38.21-65.81), while grade 3-5 RP occurred in 5.33% (95% CI, 1.87-10.41). Treatment discontinuation due to RP occurred in 17.07% of cases (95% CI, 0.00-56.86) across 3 studies involving 86 patients. Subgroup analysis showed a significant difference in RP incidence across EGFR-TKI generations (P = .0038), with first- and third-generation TKIs exhibiting higher rates (64.83% and 64.09%, respectively). Hypothesis-generating trends based on limited data suggested higher RP rates with third-generation TKIs plus conventional radiotherapy (71.43%) or first-generation TKIs plus stereotactic body radiotherapy (SBRT) (77.41%) compared with first-generation TKIs plus non-SBRT (59.88%). No significant differences were found by radiotherapy technique or treatment timing.

The incidence of RP following EGFR-TKIs combined with TRT in advanced NSCLC may be underestimated; however, the majority of these events are low-grade and clinically manageable. The severe (grade ≥ 3) RP occurs at a substantially lower rate. Preliminary subgroup findings suggest potential signals of higher RP rates with third-generation TKIs or SBRT, warranting further validation.