Clinical characteristics and progression of pre-/minimally invasive lung adenocarcinoma harboring or rearrangements: a retrospective cohort study.

BACKGROUND

Patients harboring anaplastic lymphoma kinase () or rearranged during transfection () rearrangements are usually diagnosed at a relatively late stage with nodal and distant metastasis, and rapid progression course of / fusion-positive lung cancer were well-known. However, clinical characteristics and course of pre-/minimally invasive lung adenocarcinoma harboring or fusions are poorly described. Identifying patients with gene fusions at early stage may offer surgical options that could cure those patients.

METHODS

We retrospectively included patients with surgically resected pre-/minimally invasive lung adenocarcinomas harboring epidermal growth factor receptor () mutations or / rearrangements, and further compared the patient clinical characteristics, nodule natural course, and survival outcomes. Radiological characteristics including ground-glass component, cystic airspace, pleural attachment, etc. were specially assessed for this study. (exons 18-22) was detected by Sanger sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the / rearrangements. Lung cancer-specific survival (LCSS), relapse-free survival (RFS), and overall survival (OS) were all evaluated.

RESULTS

Of 238 patients with pre-/minimally invasive lung adenocarcinomas, 226 patients had mutations, 7 patients had fusions, and 5 patients had fusions. Average age at surgery was 45.3 years for /-positive group and 52.6 years for -positive group (P=0.049). Radiologically, among the 12 patients with / fusions, the majority of lesions (10/12) manifested as mixed ground-glass opacities (mGGOs), which was significantly more prevalent when compared with patients with mutations (83.4% 24.3%, P<0.001). Moreover, a substantial proportion of cystic airspace was found in /-positive group but not in -positive group (66.7% 14.2%, P<0.001). Among four patients with / fusions undergoing surveillance over 1 year before surgery, two of them developed rapid radiologic progression. The 5-year LCSS and RFS were 100%, 100% for /-positive group, and 100%, 100% for -positive group, respectively.

CONCLUSIONS

/-positive pre-/minimally invasive lung adenocarcinomas were mostly characterized as mGGOs with cystic airspace developing rapid nodule progression, and no recurrence occurred during long-term follow-up after resection. This provides insights into proper curative surgery timing in the management of patients with gene fusions. However, these findings must be treated with caution and validated in future multi-center studies with larger sample size.