Abstract 3312: Comparison of risk factors to molecular risk stratification in Chinese early-stage non-squamous non-small cell lung cancer patients
Authors: Liang Naixin , Xue Jianchao , Zhao Ming , Li Bowen , Wang Yadong , Huang Zhicheng , Xia Yankai , Li Ruirui , Bing Zhongxing , Zheng Zhibo , Zhang Jianpeng , Wang Bin , Feng Zhe , Liu Xinyu , Li Haochen , Yu Xiaoqing , Song Yang 
Published: April 2023

Abstract
Background: Improved risk stratification for non-small cell lung cancer (NSCLC) represents a critical unmet need. A Clinical Laboratory Improvement Amendments (CLIA)-certified, 14-gene, quantitative PCR (qPCR)-based expression assay was found to better stratify mortality risk. The association of molecular risk stratification with other clinicopathological, radiomic, and genetic risk factors have not been fully identified, especially in Chinese NSCLC patients (pts).
Methods: We newly recruited 102 early-stage non-squamous NSCLC pts who had undergone complete surgical resection. RNA was extracted from tumor tissue specimens and prospective molecular risk stratification by the 14-gene prognostic assay was performed. Gene mutation status and tumor mutational burden (TMB) were evaluated. Histological sections and clinical records were reviewed for canonical prognostic indicators that have been reported to be associated with lung cancer risk.
Results: Of the 102 pts, the mean age was 55 years, 66 (64.7%) were female, and 18 (17.7%) had a smoking history. The majority of pts (84, 82.4%) were stage I, with 1 atypical adenomatous hyperplasia (AAH), 6 adenocarcinomas in situ (AIS), 1 stage II, and 2 stage III. 64 pts were deemed low-risk by molecular testing, 24 were intermediate-risk, and 14 were high-risk. The pts of AAH and AIS were all in the low-risk group. The maximum tumor diameter (MTD) in the high-risk group was the highest. There were no significant differences in age, sex, smoking status, pathologic stage, NCCN risk criteria, micropapillary or solid (MP/S) pattern, or the number of lesions between the three groups. The most common driver mutations were EGFR (65%), TP53 (28%), and RBM10 (13%). The molecular risk stratification had a significant association with TP53 (p = 0.013), TP53 loss of function (LOF, p = 0.01), KRAS (p = 0.011), and APC mutation (p = 0.05), but not with EGFR mutation and co-mutational status. TMB in the low-risk pts was significantly lower than in other pts (p = 0.007). The low-risk pts had lower SUVmax (p = 0.076), significantly lower mean CT value (p = 0.023), and mean enhanced CT value (p = 0.005) compared with others. In the NCCN low-risk pts, 25 were molecular low-risk, 12 were intermediate-risk, and 9 were high-risk. The risk stratification showed a significant association with SUVmax, TP53 mutation, and TMB in the NCCN low-risk pts. Pearson correlation showed the molecular risk score was significantly associated with MTD, TMB, SUVmax, mean CT value, mean enhanced CT value, and max CT value. SUVmax showed the strongest correlation with the risk score.
Conclusion: The molecular risk stratification by the 14-gene assay was associated with canonical prognostic indicators, like TP53 LOF, TP53, KRAS, APC mutation, TMB, mean CT value, and mean enhanced CT value. Our study provides more evidence of the clinical utility of the qPCR-based prognostic assay.
Citation Format: Naixin Liang, Jianchao Xue, Ming Zhao, Bowen Li, Yadong Wang, Zhicheng Huang, Yankai Xia, Ruirui Li, Zhongxing Bing, Zhibo Zheng, Jianpeng Zhang, Bin Wang, Zhe Feng, Xinyu Liu, Haochen Li, Xiaoqing Yu, Yang Song. Comparison of risk factors to molecular risk stratification in Chinese early-stage non-squamous non-small cell lung cancer patients [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 3312.