Abstract 4535: Clinical outcomes and molecular features of different histopathologic patterns in patients with stage IB non-squamous non-small-cell lung cancer

Abstract Background: About 15% to 20% of patients with stage IB non-small-cell lung cancer (NSCLC) may develop recurrence within 5 years. However, the use of adjuvant therapy for resected stage IB patients remains controversial. This study investigated the differences in prognosis and molecular features between different histopathologic patterns of stage IB non-squamous NSCLC (nsNSCLC) and tried to identify patients who most in need of adjuvant therapy. Methods: A total of 215 patients with completely resected pathologic stage IB (tumor size 3-4 cm) nsNSCLC from Tianjin Medical University Cancer Institute & Hospital between 2014 and 2018 were included in the study. For 130 patients, genomic profiling of tumor tissues was sequenced by a panel of 9 driver genes (OncoScreen® Focus CDx Tissue Kit, Burning Rock Biotech) and the molecular risk stratification was assessed by 14-gene quantitative PCR (qPCR) assay (DetermaRxTM, Burning Rock Biotech). Results: Among the 215 patients, 67.9% were solid/micropapillary-predominant pattern (S/MP), 40.5% had received platinum-based doublet adjuvant chemotherapy, and 5.1% had received adjuvant targeted therapy with or without chemotherapy. Patients with S/MP pattern had significantly worse DFS than those with lepidic/acinar/papillary-predominant (L/A/P) pattern (hazard ratio [HR]: 2.16, 95% confidence interval (CI): 1.28 to 3.67; P = 0.013). However, neither pattern could benefit from adjuvant therapy. EGFR mutation was successfully detected in 75 out of 126 patients (59.5%), and the positive rate in S/MP pattern was significantly lower than that in L/A/P pattern (50.6% vs 79.5%, P = 0.002). However, EGFR mutation status was not a prognostic factor for DFS in neither overall population nor different histopathologic patterns. EGFR-mutant patients showed the trend to benefit from adjuvant targeted-based therapy in the limited samples. Molecular risk stratification was successfully assessed in 99 patients, of which 37.4%, 26.3%, and 36.4% were predicted as molecularly high-risk, intermediate-risk, and low-risk patients, respectively. There were significant differences in the proportion of high- and low-risk patients between S/MP and L/A/P patterns (for high-risk: 46.2% vs 20.6%; for low-risk: 26.2% vs 55.9%; P = 0.009). The high-risk patients had significantly shorter DFS than the low-risk patients (HR, 2.93, 95% CI: 1.31-6.54; P = 0.012), especially those in S/MP pattern (HR, 3.45, 95% CI: 1.46-8.15; P = 0.017). Conclusion: Our study confirms that S/MP pattern is a significantly worse prognostic factor for DFS in nsNSCLC and that there are significant differences in molecular features between these two different histopathologic patterns. qPCR-based assay could reliably identify patients with a worse prognosis in S/MP pattern, suggesting that such patients are most likely to benefit from personalized adjuvant therapy. Citation Format: Dongsheng Yue, Bin Zhang, Chen Chen, Qiang Zhang, Xinyi Wu, Jiping Xie, Changli Wang, Zhenfa Zhang. Clinical outcomes and molecular features of different histopathologic patterns in patients with stage IB non-squamous non-small-cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4535.