Assessment of Early Detection by Multi-omics-Based Liquid Biopsy in Lung Cancer: A Prospective Study (ASCEND-LUNG)

Liquid biopsy offers an optimal approach for the early detection of lung cancer that is the leading cause of cancer mortality worldwide. Here, we report the results of AssesSment of early-deteCtion basEd oN liquiD biopsy in LUNG cancer (ASCEND-LUNG, NCT04817046), a prospective study designed to develop early detection models for lung cancer based on multi-omics assays including cell-free DNA (cfDNA) methylation, mutation, and tumor proteins. Blood samples from lung cancer patients were prospectively collected from Peking University People's Hospital since February 2021 (data cut-off December 15, 2021). Age matched non-cancer controls were selected. A methylation panel of ∼490,000 CpG sites sequenced by the ELSA-seq, a mutation panel of ultradeep sequenced 168 genes, and tumor protein assays were performed. Early detection models were developed by 5-fold cross validation. In total, the multi-omics data of 158 patients with lung cancer and 135 non-cancer controls were included in the model development. The specificities for methylation, mutation, and protein models were 98.5% (95% CI, 95.6%‒100%), 100% (97.8%‒100%) and 100% (97.8%‒100%), respectively. The sensitivities of them were 72.8% (65.2%‒79.1%), 18.8% (12.5%‒26.8), and 32.1% (25.0%‒39.7%), respectively. Combing all three models could improve the performance of early detection with a sensitivity of 83.8% (76.6%‒90.1%) and a specificity of 98.5% (95.6%‒100%).Table: 910PPerformance of the early detection models for lung cancerPerformanceEarly detection models for lung cancerMulti-omicsMethylationMutationProteinSpecificity (95%CI)98.5% (95.6‒100%)98.5% (95.6‒100%)100% (97.8‒100%)100% (97.8‒100%)Sensitivity (95%CI)Total83.8% (76.6‒90.1%)72.8% (65.2‒79.1%)18.8% (12.5‒26.8%)32.1% (25.0‒39.7%)Stage I79.7% (67.8‒89.8%)65.0% (53.8‒75.0%)1.7% (0‒6.8%)25.3% (16.5‒35.4%)Stage II77.8% (55.6‒94.4%)70.4% (51.9‒85.2%)26.3% (10.5‒47.4%)34.6% (15.4‒53.8%)Stage III96.0% (88.0‒100%)87.5% (75.0‒97.5%)40.0% (20.0‒60.0%)35.0% (20.0‒50.0%)Stage IV88.9% (66.7‒100%)81.8% (54.5‒100%)55.6% (22.2‒88.9%)63.6% (36.4‒90.9%) Open table in a new tab In this study, the methylation-based lung cancer early detection model showed superior performance compared with the models based on mutation or protein. The multi-omics combined model can further improve the sensitivity at a considerably high specificity. Our study highlights a potential clinical utility of the multi-omics-based early detection model for lung cancer. The enrollment of validation set is ongoing and expected to be completed by March 2023.