Comparison of post-chemoradiotherapy pneumonitis between Asian and non-Asian patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis

BACKGROUND: Pneumonitis is a common complication for patients with locally advanced non-small cell lung cancer undergoing definitive chemoradiotherapy (CRT). It remains unclear whether there is ethnic difference in the incidence of post-CRT pneumonitis. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched for eligible studies from January 1, 2000 to April 30, 2023. The outcomes of interest were incidence rates of pneumonitis. The random-effect model was used for statistical analysis. This meta-analysis was registered with PROSPERO (CRD42023416490). FINDINGS: A total of 248 studies involving 28,267 patients were included. Among studies of CRT without immunotherapy, the pooled rates of pneumonitis for Asian patients were significantly higher than that for non-Asian patients (all grade: 66.8%, 95% CI: 59.2%–73.9% vs. 28.1%, 95% CI: 20.4%–36.4%; P < 0.0001; grade ≥2: 25.1%, 95% CI: 22.9%–27.3% vs. 14.9%, 95% CI: 12.0%–18.0%; P < 0.0001; grade ≥3: 6.5%, 95% CI: 5.6%–7.3% vs. 4.6%, 95% CI: 3.4%–5.9%; P = 0.015; grade 5: 0.6%, 95% CI: 0.3%–0.9% vs. 0.1%, 95% CI: 0.0%–0.2%; P < 0.0001). Regarding studies of CRT plus immunotherapy, Asian patients had higher rates of all-grade (74.8%, 95% CI: 63.7%–84.5% vs. 34.3%, 95% CI: 28.7%–40.2%; P < 0.0001) and grade ≥2 (34.0%, 95% CI: 30.7%–37.3% vs. 24.6%, 95% CI: 19.9%–29.3%; P = 0.001) pneumonitis than non-Asian patients, but with no significant differences in the rates of grade ≥3 and grade 5 pneumonitis. Results from subgroup analyses were generally similar to that from the all studies. In addition, the pooled median/mean of lung volume receiving ≥20 Gy and mean lung dose were relatively low in Asian studies compared to that in non-Asian studies. INTERPRETATION: Asian patients are likely to have a higher incidence of pneumonitis than non-Asian patients, which appears to be due to the poor tolerance of lung to radiation. Nevertheless, these findings are based on observational studies and with significant heterogeneity, and need to be validated in future large prospective studies focusing on the subject. FUNDING: None.