The following is a summary of “Comparison of risk factors to molecular risk stratification in Chinese early-stage non-squamous non-small cell lung cancer patients,” published in the April 2023 issue of Oncology by Liang, et al.

An important unmet need is the development of more accurate risk classification methods for non-small cell lung cancer (NSCLC). Better risk stratification was reported to be achieved by using a 14-gene quantitative PCR (qPCR)-based expression assay, which met the requirements of the Clinical Laboratory Improvement Amendments (CLIA). In NSCLC patients (pts), the connection between molecular risk stratification and other clinicopathological, radiomic, and genetic risk factors is poorly understood. Researchers enrolled 102 patients who had undergone complete surgical resection for early-stage non-squamous NSCLC. RNA was extracted from the tumor samples, and the 14-gene prognostic assay was used to stratify the molecular risk prospectively. Tumor mutational burden (TMB) and gene mutation status were analyzed. 

Standard prognostic markers reported to be related to lung cancer risk were culled from reviews of histological sections and patient medical files. There were 102 points, with a mean age of 55 years, 66 (64.7%) being female, and 18 (17.7%) reporting a smoking history. About 84 patients (82.4% of the total) were diagnosed with stage I disease; 1 had atypical adenomatous hyperplasia (AAH), and 6 had adenocarcinomas in situ (AIS). After analyzing molecular data, 64 patients were classified as low risk, 24 as intermediate, and 14 as high. All the AAH and AIS patients were considered to be low-risk. Maximum tumor diameter (MTD) was the largest in the high-risk cohort. Micropapillary or solid (MP/S) pattern, several lesions, age, sex, smoking status, pathologic stage, NCCN risk criteria, and NCCN risk criteria were all comparable across the 3 groups. Mutations in EGFR (65%), TP53 (28%), and RBM10 (13%) were the most prevalent drivers. There was a substantial correlation between molecular risk stratification and TP53 (P=0.013), TP53 LOF (P=0.01), KRAS (P=0.011), and APC mutation (P=0.05), but not with EGFR mutation and co-mutational status. 

Much less TMB was seen in the low-risk pts than in the other pts (P=0.007). The SUVmax was also lower in the low-risk pts (P=0.076), as was the mean CT value (P=0.023) and the mean enhanced CT value (P=0.005). For every 25 patients classified as low risk by the NCCN, 12 were classified as intermediate risk, and 9 were classified as high risk. SUVmax, TP53 mutation status, and TMB were significantly correlated in NCCN low-risk patients, as determined by the risk classification. There was a statistically significant relationship between the molecular risk score and MTD, TMB, SUVmax, mean CT value, mean enhanced CT value, and maximum CT value, as determined by Pearson correlation. There was a significant relationship between SUVmax and risk score. Canonical prognostic markers, such as TP53 LOF, TP53, KRAS, APC mutation, TMB, mean CT value, and mean increased CT value, were correlated with the molecular risk classification using the 14-gene assay. The findings further support the therapeutic relevance of the qPCR-based prognostic assay.