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Kaplan-Meier survival analysis showed that ECOG PS, brain metastasis, SIRI were significantly correlated with progression-free survival (PFS), and gender, ECOG PS, brain metastasis, NLR and SIRI were significantly correlated with overall survival (OS). Multivariate analysis showed that SIRI and ECOG PS independently predict PFS and OS. Our findings indicate that SIRI is an effective and convenient marker for predicting prognosis in advanced EGFR-mutant lung adenocarcinoma patients treated with first-generation TKI. Our findings indicate th