Clinical Outcomes And Radiation Pneumonitis After Concurrent Egfr-Tyrosine Kinase Inhibitors And Radiotherapy For Unresectable Stage Iii Non-Small Cell Lung Cancer

Background: Concurrent epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with radiotherapy in patients with EGFR-mutant unresectable stage III non-small cell lung cancer (NSCLC) might improve survival. However, both treatments carry a potential risk of pneumonitis.Methods: Between May 2012 and December 2017, patients with unresectable stage III NSCLC treated with concurrent radiotherapy and EGFR-TKI were enrolled in this retrospective study. The baseline characteristics were evaluated to determine correlations with toxicity development.Results: Among 45 eligible patients, 20 (44.4%) had an EGFR mutation and 44 (97.8%) received 50-66 Gy of radiotherapy. The median follow-up was 62.7 months. The median progression free survival (PFS) and overall survival (OS) for patients with EGFR-mutations were 27.9 (95% CI: 18.7-37.2) and 49.7 (95% CI: 27.7-71.8) months, and 13.8 (95% CI: 8.8-18.9) and 31.1 (95% CI: 9.8-52.4) months for EGFR wild-type/unknown patients. A total of 17 patients (37.7%) developed radiation pneumonitis/pneumonitis (14 grade 2, 3 grade 3). In 16 patients, pneumonitis occurred within the radiation field and one patient had bilateral pneumonitis. The median time from the initial radiotherapy to pneumonitis was 74 days. Logistic regression analysis revealed a trend between the time of EGFR-TKI and the development of G2+ pneumonitis. For late toxicity, only two patients had G2+ fibrosis. The daily dyspnea symptoms of patients with G2+ pneumonitis recovered significantly after the phase of pneumonitis (P = 0.007).Conclusions: Combined EGFR-TKI and radiotherapy showed favorable survival in EGFR-mutant patients with inoperable stage III NSCLC, with a 6.7% incidence of grade 3 radiation pneumonitis/pneumonitis, despite a higher incidence of mild-to-moderate radiation pneumonitis.Key pointsSignificant findings of the study: We evaluated the outcomes and radiation pneumonitis after EGFR-TKI during interval radiotherapy. EGFR-TKI plus radiotherapy increased survival in patients with EGFR-mutant inoperable stage III NSCLC. The mild-to-moderate radiation pneumonitis incidence increased but no grade 4--5 adverse events occurred.What this study adds: The combination of EGFR-TKI and radiotherapy might carry a risk of pneumonitis; however, there are limited data concerning dose constraints. Our results showed a slightly higher incidence of mild or moderate radiation pneumonitis by strict dose limitation.