Abstract:

Objective To assess stromal fibrosis in epidermal growth factor receptor （EGFR） mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis. Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed. A total of 86 patients were ultimately included based on their prognosis and survival duration. These patients were categorized into a resistance group （32 cases） and a non-resistance group （54 cases）， depending on whether they developed resistance to targeted therapy within one year. Additionally， patients were classified into mild， moderate， and severe fibrosis groups according to the extent of fibrosis observed. Clinical and pathological characteristics， as well as fibrosis levels， were compared between the two groups. Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed， and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up. Results In the resistance group， the prevalence of EGFR exon 20 insertion mutations， elevated CA125 levels， and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group （P < 0.05）. Multivariate logistic regression analysis revealed that EGFR exon 20 insertion mutation （OR = 3.691， 95%CI： 1.043 ~ 13.057）， elevated CA125 levels （OR = 4.104， 95%CI： 1.160 ~ 14.517）， and moderate-to-severe fibrosis （OR = 3.959， 95%CI： 1.410 ~ 11.115） were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma （P < 0.05）. The Cox proportional hazards model demonstrated a C-index of 0.72 （95%CI： 0.65 ~ 0.79）， with area under the curve （AUC） values for 1-year and 2-year survival predictions of 0.781 and 0.734， respectively. EGFR exon 20 insertion mutation （HR = 3.691）， moderate-to-severe fibrosis （HR = 3.959）， and elevated CA125 levels （HR = 4.104） were identified as independent prognostic factors for overall survival in these patients following targeted therapy. The median progression-free survival （PFS） for patients with mild， moderate， and severe fibrosis was 10.5 months， 7.2 months， and 3.9 months， respectively， while the median overall survival （OS） was 21.4 months， 16.1 months， and 11.5 months， respectively. Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups. （P < 0.05）. Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy， and the progression of fibrosis is correlated with an unfavorable prognosis.

Key words: lung adenocarcinoma, EGFR mutation, stromal fibrosis degree, targeted therapy resistance, survival prognosis