Imaging Pattern of Diffuse Intrapulmonary Metastases in Lung Cancer Was Associated with Poor Prognosis to Epidermal Growth Factor Receptor Inhibitors

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are more frequently seen in miliary intrapulmonary metastases than EGFR wild-type non-small cell lung cancer (NSCLC). Also, small-scale retrospective studies showed that patients harboring EGFR mutation with miliary pulmonary metastases had a worse prognosis. This study aimed to explore the impact of imaging patterns on the outcomes of EGFR tyrosine kinase inhibitor (TKI) treatment. METHODS: A cohort of treatment-naive NSCLC patients harboring EGFR mutation with intrapulmonary metastases who were prescribed with TKI were enrolled. The demographic feature, clinical outcome, and CT imaging of each patient were reviewed and analyzed. RESULTS: A cohort of 174 patients were enrolled. Five intrapulmonary patterns of imaging were recognized: solid nodular, ground-glass nodular, miliary, multiple uniform nodular, and not otherwise specified. Among them, miliary and multiple uniform nodular patterns had similar poor prognosis, and, therefore, were combined as diffuse group. A worse PFS (9.0 mon, 95% CI: 8.0–10.0 mon) was observed compared with the rest (non-diffuse group, 13.3 mon, 95% CI: 10.2–16.4 mon, p<0.001, HR=0.49). The objective response rates (ORR) between the two groups were 76.8% and 84.1%, respectively, with no significant difference (p = 0.474). The OS of the diffuse and the non-diffuse group were 25.6 mon (95% CI 21.9–29.3 mon) and 35.0 mon (95% CI: 27.5–42.5, p = 0.01, HR= 0.59). Organs like bone (p=0.167), liver (p=0.513), and adrenal gland (p=0.375) were involved in similar frequencies in both groups. However, brain (p=0.070) and leptomeningeal (p=0.078) metastases were less common in the non-diffuse group with marginally statistical significance. The 2 groups contained similar missense mutations, and gene amplification was more common in the non-diffuse group. CONCLUSION: Patients with diffuse intrapulmonary metastases had inferior outcomes after TKI treatment. More aggressive treatments might be warranted for these patients.